Genitourinary Cancer

Metastatic Renal Cell Carcinoma - First Line

First Line
- VICCURO21103
  Optimal Treatment by Invoking Biologic Clusters in Renal Cell Carcinoma (OPTIC RCC)
  - Metastatic, measurable clear cell RCC without prior systemic tx in any setting.
    Tumor tissue available for RNA-sequencing (metastatic preferred, no bone)
    Calculated creatinine clearance ≥30 mL/min per the Cockcroft Gault
    No immunosuppressive meds or prednisone equivalent > 10mg/d
    **FYI time from consent to first treatment day likely 3-4 weeks
- ALLIANCEUROA031702
  A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
  - Key Eligibilty Criteria:
    Inclusion:
    1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
    a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
    b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
    - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
    - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
    - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
    - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
    - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
    - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
    c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
    2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
    3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
    4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
    5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
- VICCURO24517
  Phase 2 Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in 1L aRCC
  - Key Eligibility Criteria:
    
    Inclusion Criteria:
    1. Histological or cytological evidence of renal cell carcinoma having a clear cell component.
    2. Advanced (not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma
    3. Treatment naïve for systemic therapy for renal cell carcinoma including no prior neo/adjuvant systemic therapy
    4. Archival tissue available.
    
    Exclusion Criteria:
    1. Prior systemic therapy against renal cell carcinoma in the neo/adjuvant or metastatic setting
    2. Participants with a history of myocarditis.
    
    For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL
- VICCURO25011
  Phase 1b/2 Study of Immune and Targeted Therapies in Participants with Recurrent RCC after Adjuvant
  - Key Eligibility Criteria:
    
    Inclusion Criteria:
    1. Confirmed diagnosis of unresectable locally advanced/metastatic RCC with clear cell component.
    2. Has received no other prior systemic therapy for treatment of advanced/metastatic ccRCC, except for adjuvant anti-PD-(L)1 therapy.
    3. Has disease recurrence during adjuvant anti-PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy.
    4. Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
    
    Exclusion Criteria:
    1. Deep vein thrombosis within 3 months before allocation/randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before allocation/randomization.
    2. Prolongation of QTcF interval to >480 ms.
    3. Received prior treatment with HIF-2alpha and/or VEGF/TKI inhibitors.
    4. Have been previously allocated/randomized to study intervention in any sub-study of protocol MK-3475-U03.
    5. Has any of the following:
    a. A pulse oximeter reading <92% at rest, or
    b. Requires intermittent supplemental oxygen, or
    c. Requires chronic supplemental oxygen.
    
    For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL

Metastatic Renal Cell Carcinoma - Refractory

Refractory
- 2nd - 3rd line
  - ALLIANCEUROA031702
    A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
    - Key Eligibilty Criteria:
      Inclusion:
      1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
      a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
      b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
      - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
      - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
      - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
      - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
      - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
      - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
      c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
      2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
      3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
      4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
      5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
  - VICCURO24575
    Phase 3 Study of Casdatifan & Cabozantinib vs Placebo & Cabozantinib in ccRCC
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      
      1. Unresectable locally advanced or metastatic renal cell carcinoma with a primary clear cell component.
      2. Must have received anti-PD-1 or anti-PD-L1 therapy as part of the most recent regimen (either adjuvant monotherapy or first-line in combination with anti-CTLA-4 or VEGFR-TKI), with no more than 1 prior regimen in the metastatic setting.
      a) Patients must have received at least 2 doses of anti-PD-1 or anti-PD-L1 therapy.
      b) For patients who received anti-PD-1 in adjuvant setting, radiographic progression must have occurred on or within 12 months of last dose.
      
      Exclusion Criteria:
      1. Received prior treatment with a HIF-2α inhibitor.
      2. Received prior treatment with cabozantinib.
      3. Concomitant treatment with therapeutic doses of anticoagulants such as heparin, warfarin, thrombin, or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel).
      Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and prophylactic low molecular weight heparin (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in patients who are on a stable dose of LMWH for at least 1 week before administration of the first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
      4. Uncontrolled or poorly controlled hypertension, as defined by a sustained blood pressure > 140/90 mm Hg on more than three antihypertensives.
      Note: Blood pressure medication may not be started nor changed within the 14 days prior to randomization.
      
      For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL
  - VICCURO25-03
    A Pilot Study of HIF-Mediated Gene Expression Changes in Casdatifan-Treated Refractory RCC
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Histologically confirmed metastatic clear cell renal cell carcinoma (ccRCC).
      2. Patients must have received at least one immune-oncology (IO) agent and at least one VEGF-targeted therapy (alone or in combination).
      3. No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry </= 88%.
      4. No active pneumonitis at screening as assessed by CT scan.
      5. No medical history of severe chronic obstructive pulmonary disease (COPD).
      
      Exclusion Criteria:
      1. Prior treatment with HIF-2α inhibitors (e.g. belzutifan or related agents).
      2. Contraindications to biopsy (e.g. bleeding diathesis, uncorrectable coagulopathy).
      
      For internal pre-screening, please contact: Epic message basket- VICC RESEARCH UROTHELIAL
- 2nd - 4th line
- 2nd - 5th line
- 2nd line and beyond
  - VICCURO25-03
    A Pilot Study of HIF-Mediated Gene Expression Changes in Casdatifan-Treated Refractory RCC
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Histologically confirmed metastatic clear cell renal cell carcinoma (ccRCC).
      2. Patients must have received at least one immune-oncology (IO) agent and at least one VEGF-targeted therapy (alone or in combination).
      3. No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry </= 88%.
      4. No active pneumonitis at screening as assessed by CT scan.
      5. No medical history of severe chronic obstructive pulmonary disease (COPD).
      
      Exclusion Criteria:
      1. Prior treatment with HIF-2α inhibitors (e.g. belzutifan or related agents).
      2. Contraindications to biopsy (e.g. bleeding diathesis, uncorrectable coagulopathy).
      
      For internal pre-screening, please contact: Epic message basket- VICC RESEARCH UROTHELIAL
  - VICC-DTPHI24194
    Phase 1 study of DCC-2812 in Advanced or Metastatic RCC, UC, or CRPC
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Must have one of the following diagnoses under study:
      a. RCC: Have histologically or cytologically confirmed advanced or metastatic RCC and have progressed on, are intolerant to, or have a contraindication to treatment with a VEGFR-TKI and an anti-PD-(L)1 antibody.
      b. Urothelial carcinoma: Have histologically or cytologically confirmed advanced or metastatic urothelial carcinoma and have progressed on, are intolerant to, or have a contraindication to treatment with an anti-PD-(L)1 antibody and enfortumab vedotin-ejfv. Participants with susceptible FGFR3 or FGFR2 tumor genetic alterations must have progressed on, be intolerant to, or have a contraindication to treatment with an FGFR inhibitor, if approved and available in the study site's region.
      c. Castration-resistant prostate cancer: Have a histologically or cytologically confirmed advanced or metastatic prostate cancer after treatment with at least 1 androgen receptor signaling inhibitor (such as abiraterone, enzalutamide, apalutamide, and darolutamide). Participants with prostate cancer must also fulfill both of the following:
      i. Ongoing androgen deprivation from prior orchiectomy or continued luteinizing hormone-releasing hormone agonist or antagonist therapy with leuprolide, goserelin, buserelin, triptorelin, or degarelix and a Screening testosterone level of 50 ng/dL or less.
      ii. At least 1 metastatic lesion outside the prostate and at least one of the following: any soft tissue lesion that is measurable according to RECIST v1.1 and/or a PSA level of at least 1 ng/mL.
      
      Exclusion Criteria:
      1. Has history of systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or moderate hemoptysis within 6 months prior to the first dose of study drug.
      2. Has history of systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) unless they have been on stable anticoagulation for at least 30 days or the event has completely resolved and there is no need for ongoing treatment.
      
      For pre-screening, please contact: VICC RESEARCH PHASE 1
- Any Line

Renal Adjuvant

Adjuvant
- ALLUROA032201
  Short Term Intensified Pembrolizumab (Keytruda) and Tivozanib for High-Risk Renal Cell Carcinoma
  - Key Eligibility Criteria:
    
    Inclusion:
    1.Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features following complete resection of the primary tumor (radical or partial nephrectomy).
    2. Note: Patients with microscopically positive soft tissue or vascular margins without gross residual disease are permitted.
    a. Intermediate-high risk RCC:
    i. pT2 Grade 4 or sarcomatoid features, N0M0
    ii. pT3 any grade N0, M0
    b. High-risk RCC:
    i. pT4, any grade, N0, M0
    ii. pT, any stage., any grade, N+, M0
    c. cM1 NED RCC:
    i. Participants who have had resection of primary tumor (radical or partical nephrectomy) and resection or definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) at the time of primary tumor removal (synchronous) or ≤1 year from primary tumor removal (metachronous).
    3. Surgery (radical or partial nephrectomy or metastasectomy or ablation) >4 weeks but ≤ 16 weeks prior to study registration with no ongoing complications from surgery
    4. No evidence of disease at time of randomization as assessed by investigator by either CT or MRI scan of the brain and chest, abdomen and pelvis
    5. No prior systemic treatment for RCC
    
    For pre-screening, please contact: Please reach out to the Disease specific research teams.

Prostate - Advanced

Castration Sensitive
- Metastatic
  - SWOGUROS1802
    Standard Systemic Therapy (SST) +/- Definitive Treatment in Metastatic Prostate Cancer
    - Key Eligibility
      1. Metastatic (conventional imaging; if only PET then bx required) prostate adenoca with an intact and resectable prostate.
      2. Between 22 - 28 weeks of SST, without PD
      3. No prior local therapy or other systemic therapy allowed
      4. Oligometastatic disease may receive metastasis directed therapy to up to four sites
      5. Visits every 3 months through 24 months, then every 6 months at M30, M36, until progression
  - ALLUROCCTGPR26
    Docetaxel to Androgen Receptor Pathway Inhibitors in Metastatic Prostate Cancer and Suboptimal PSA
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Histologically/cytologically confirmed adenocarcinoma of prostate.
      2. Metastatic disease by conventional imaging.
      3. PSA of >/= 5.0 ng/ml (5.0 ug/L) prior to commencement of ADT.
      4. Prior Therapy
      a. Systemic Therapy
      i. Receipt of ADT for mCSPC for at least 6 months and no greater than 12 months at time of enrollment.
      ii. Receipt of ARPI (e.g. abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for at least 4 months at time of enrollment.
      b. Radiotherapy
      i. Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
      5. Serum testosterone < 1.7 nmol/L or 50 ng/dL.
      6. PSA >/= 0.2 ng/ml (0.2 ug/L) within 14 days of enrollment.
      7. Candidate for docetaxel chemotherapy (per investigator).
      
      Exclusion Criteria:
      1. Two consecutive rises in PSA since achieving castration on ADT at least 2 weeks apart with at least one PSA >/= 5% above the PSA nadir and with at least one PSA having an absolute increase of >/= 0.5 ng/ml above the PSA nadir.
      2. Evidence of radiographic progression or clinical progression since start of ADT.
      3. High-grade neuroendocrine prostate cancer or small cell features.
Castration Resistant
- Non-metastatic
  - SWOGGIS2012
    Platinum/Etoposide w or w/o Atezolizumab in Pts w/Poorly Diff Extrapulmonary Small Cell NEC
    - Inclusion Criteria:
      1. Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC).
      2. Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator.
      3. Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinumbased therapy +/- radiation +/- surgery provided that all therapy was completed >/= 6 months prior to registration.
      4. Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >/= 24 weeks prior to registration and participants have recovered from all prior toxicities to </= grade 1.
      5. Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least
      12 months prior to study registration.
- Metastatic
  - ALLUROA032102
    Precision Diagnostics in Prostate Cancer Treatment (PREDICT)
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Histological or cytological evidence of prostate cancer. Patients with variant histologies including neuroendocrine, small cell and sarcomatoid prostate cancer are allowed to enroll and these will not be used as selection criteria for individual arms.
      2. Tissue procured within 12 months of pre-registration (metastatic disease preferred over primary tissue, though both are acceptable) available for submission.
      3. Molecular report available performed as part of standard of care testing. Patients may be assigned based on pre-determined qualifying molecular/DNA alterations after receipt of local molecular testing. Final determination of arm assignment will be determined by the MTB. If no qualifying DNA alteration is identified, Caris testing should be performed for both DNA/RNA profiling.
      4. Progressive mCRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND one or more of the following criteria (choose all the apply):
      5. PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 2.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy.
      6. Radiographic progression per RECIST 1.1 criteria for soft tissue lesions
      7. Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
      8. Prior treatment with ARSI in either the metastatic hormone sensitive setting or mCRPC is required. Prior taxane therapy in either metastatic hormone sensitive setting or mCRPC is mandated unless patient is taxane ineligible or the patient refuses taxane therapy. Prior lutetium LU177 vipivotide tetraxetan treatment is permitted but not mandated. Patients with known germline or somatic deleterious BRCA 1/2 mutations must have received a prior PARPi.
      9. No prior treatment with EZH inhibitors.
  - VICC-DTPHI24194
    Phase 1 study of DCC-2812 in Advanced or Metastatic RCC, UC, or CRPC
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Must have one of the following diagnoses under study:
      a. RCC: Have histologically or cytologically confirmed advanced or metastatic RCC and have progressed on, are intolerant to, or have a contraindication to treatment with a VEGFR-TKI and an anti-PD-(L)1 antibody.
      b. Urothelial carcinoma: Have histologically or cytologically confirmed advanced or metastatic urothelial carcinoma and have progressed on, are intolerant to, or have a contraindication to treatment with an anti-PD-(L)1 antibody and enfortumab vedotin-ejfv. Participants with susceptible FGFR3 or FGFR2 tumor genetic alterations must have progressed on, be intolerant to, or have a contraindication to treatment with an FGFR inhibitor, if approved and available in the study site's region.
      c. Castration-resistant prostate cancer: Have a histologically or cytologically confirmed advanced or metastatic prostate cancer after treatment with at least 1 androgen receptor signaling inhibitor (such as abiraterone, enzalutamide, apalutamide, and darolutamide). Participants with prostate cancer must also fulfill both of the following:
      i. Ongoing androgen deprivation from prior orchiectomy or continued luteinizing hormone-releasing hormone agonist or antagonist therapy with leuprolide, goserelin, buserelin, triptorelin, or degarelix and a Screening testosterone level of 50 ng/dL or less.
      ii. At least 1 metastatic lesion outside the prostate and at least one of the following: any soft tissue lesion that is measurable according to RECIST v1.1 and/or a PSA level of at least 1 ng/mL.
      
      Exclusion Criteria:
      1. Has history of systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or moderate hemoptysis within 6 months prior to the first dose of study drug.
      2. Has history of systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) unless they have been on stable anticoagulation for at least 30 days or the event has completely resolved and there is no need for ongoing treatment.
      
      For pre-screening, please contact: VICC RESEARCH PHASE 1
  - VICCURO25040
    Phase 2 Trial of Fam-Trastuzumab Deruxtecan-Nxki as Subsequent Tx in HER2+ mCRPC
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Pathologically confirmed adenocarcinoma of the prostate.
      2. Diagnosis of mCRPC.
      3. Documented progression on androgen deprivation and novel hormonal agents, with or without progression on taxane containing regimen.
      4. Ongoing ADT to maintain serum testosterone levels below 50 ng/dL.
      5. Formalin fixed paraffin embedded tumor tissue for HER2 immunohistochemistry.
      
      Exclusion Criteria:
      1. History of interstitial lung disease or pneumonitis requiring steroids
      2. Significant coronary vascular disease
      3. Previous exposure to HER2 targeted therapy
      
      For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL
  - VICCURO24538
    Phase 2 CD46-Targeted Antibody-Drug (FG-3246) in Metastatic Castration-Resistant Prostate Cancer
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Participants must have histological, and/or cytological confirmation of prostate adenocarcinoma.
      2. Participants with safely accessible tumor lesion must agree to biopsy of a primary or metastatic lesion during screening. They may provide an archival biopsy of a primary or metastatic lesion that was taken after castration resistance developed and within 1 year prior to randomization.
      3. Participants must have serum testosterone levels <50 ng/dL during screening.
      4. Participants are required to have progressed on one prior treatment with a second-generation ARSI initiated in either the castration-sensitive or castration-resistant setting.
      5. Participant must have progressive mCRPC following last treatment at screening.
      
      Exclusion Criteria:
      1. Participant has received previous treatment with a therapeutic targeting CD46.
      2. Participant has small cell neuroendocrine carcinoma (pure or mixed) or any other non-adenocarcinoma component on prior or current histologic evaluation of primary or metastatic lesion.
      3. Participant has received more than one prior second-generation ARSI in any setting.
      4. Participant has a known actionable mutation or gene alteration.
      
      For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL
  - VICCURO24539
    Phase 3 Study of Infinatamab Deruxtecan vs Docetaxel in mCRPC
    - Key Eligibility Criteria:
      
      Inclusion Criteria:
      1. Has prostate cancer progression while on ADT (or post bilateral orchiectomy) within 6 months prior to Screening, as determined by the investigator, by means of one or more of the following:
      a) Clinical disease progression and with PSA progression using local laboratory values as defined by a minimum of 2 consecutive rising PSA levels with an interval of >/=1 week between each assessment where the PSA value at Screening should be >/=1 ng/mL.
      b) Radiographic disease progression in soft tissue based on RECIST 1.1 criteria.
      c) Radiographic disease progression in bone based on PCWG3, defined as the appearance of 2 or more new bone lesions on bone scan.
      2. Has progression under the following conditions if the participant received first generation antiandrogen therapy prior to enrollment:
      a) Evidence of progression >4 weeks since last flutamide treatment.
      b) Evidence of progression >6 weeks since last bicalutamide or nilutamide treatment.
      3. Has received prior treatment with 1 or 2 ARPI(s) for nmHSPC, mHSPC, nmCRPC, or mCRPC and progressed during or after at least 8 weeks of treatment.
      4. Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM). If the participant is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists, this therapy must have
      been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study.
      5. Has had prior treatment with PARPi if indicated by local approved regimen or were deemed ineligible to receive treatment by the investigator.
      
      Exclusion Criteria:
      1. Clinically significant corneal disease.
      2. All of the following indicators of ILD/pneumonitis are excluded:
      a) Any history of ILD/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids
      b) Current diagnosis of ILD
      c) Clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out.
      3. Has received prior treatment with a taxane-based chemotherapy agent for mCRPC
      4. Prior treatment with orlotamab, enoblituzumab, or other B7-H3-targeted agents, including I-DXd.
      5. Prior discontinuation of an ADC that consists of an exatecan derivative due to treatment-related toxicities.
      
      For pre-screening, please contact:
      Message Basket: VICC RESEARCH UROTHELIAL
Treatment Naive

Bladder - Metastatic

1st Line
- ALLIANCEUROA031702
  A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
  - Key Eligibilty Criteria:
    Inclusion:
    1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
    a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
    b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
    - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
    - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
    - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
    - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
    - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
    - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
    c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
    2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
    3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
    4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
    5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
- VICCURO24518
  Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
  - Key Eligibility Criteria:
    Inclusion Criteria:
    1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
    2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
    a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
    b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
    c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
    d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
    3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
    a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
    4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
    
    Exclusion Criteria:
    1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
    2. For Cohort B5 only, individuals with known uncontrolled diabetes.
    3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
    4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
    
    For pre-screening, please contact: Individual disease research teams.
2nd line and Above
- Prior treatment with PD-1 or PD-L1 in locally advanced or metastatic setting
  - VICCURO24518
    Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
      2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
      a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
      b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
      c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
      d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
      3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
      a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
      4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
      
      Exclusion Criteria:
      1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
      2. For Cohort B5 only, individuals with known uncontrolled diabetes.
      3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
      4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
      
      For pre-screening, please contact: Individual disease research teams.
  - VICC-DTPHI23103
    A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults with Select Solid Tumors
    - Key Eligibility Criteria:
      
      Inclusion:
      1. For Phase 1b: locally advanced, recurrent, or metastatic, incurable, and histologically or cytologically confirmed HR+/HER2- breast cancer by ASCO/CAP criteria (based on most recent assessment):
      a) Must have received CDK4/6i in the adjuvant or metastatic setting, unless patient was unable or unwilling to receive standard of care CDK4/6i treatment; or must be able to receive it on protocol, AND,
      b) Received no more than 1 prior line of therapy containing chemotherapy (including cytotoxic antibody-drug conjugates) given in the metastatic setting; AND,
      c) Must have received no more than 3 lines of therapy in total for metastatic disease.
      d) May have received a prior PI3Ka inhibitor
      
      NOTE: If the patient progressed on the PI3K inhibitor a sample (tissue or liquid) must have been obtained following progression, or at study screening, to be analyzed at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory, determine the resistance mutation(s) and Sponsor approval for study inclusion obtained. If the patient was intolerant to the drug, then mutational analysis and Sponsor approval are not required for enrollment.
      
      Exclusion:
      1. Has had tumor evaluated for PTEN and AKT and has known mutations or deletions in PTEN, or, activating mutations in AKT (E17K) determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory (e.g., ISO15189-certified, in-house clinical testing).
      2. Metaplastic breast cancer
      3. Possible allergies to TOS-358 or excipients
      
      For pre-screening, please contact: Message Basket: P VICC RESEARCH BREAST OHO
  - VICC-DTPHI24194
    Phase 1 study of DCC-2812 in Advanced or Metastatic RCC, UC, or CRPC
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Must have one of the following diagnoses under study:
      a. RCC: Have histologically or cytologically confirmed advanced or metastatic RCC and have progressed on, are intolerant to, or have a contraindication to treatment with a VEGFR-TKI and an anti-PD-(L)1 antibody.
      b. Urothelial carcinoma: Have histologically or cytologically confirmed advanced or metastatic urothelial carcinoma and have progressed on, are intolerant to, or have a contraindication to treatment with an anti-PD-(L)1 antibody and enfortumab vedotin-ejfv. Participants with susceptible FGFR3 or FGFR2 tumor genetic alterations must have progressed on, be intolerant to, or have a contraindication to treatment with an FGFR inhibitor, if approved and available in the study site's region.
      c. Castration-resistant prostate cancer: Have a histologically or cytologically confirmed advanced or metastatic prostate cancer after treatment with at least 1 androgen receptor signaling inhibitor (such as abiraterone, enzalutamide, apalutamide, and darolutamide). Participants with prostate cancer must also fulfill both of the following:
      i. Ongoing androgen deprivation from prior orchiectomy or continued luteinizing hormone-releasing hormone agonist or antagonist therapy with leuprolide, goserelin, buserelin, triptorelin, or degarelix and a Screening testosterone level of 50 ng/dL or less.
      ii. At least 1 metastatic lesion outside the prostate and at least one of the following: any soft tissue lesion that is measurable according to RECIST v1.1 and/or a PSA level of at least 1 ng/mL.
      
      Exclusion Criteria:
      1. Has history of systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or moderate hemoptysis within 6 months prior to the first dose of study drug.
      2. Has history of systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) unless they have been on stable anticoagulation for at least 30 days or the event has completely resolved and there is no need for ongoing treatment.
      
      For pre-screening, please contact: VICC RESEARCH PHASE 1
- ALLIANCEUROA031702
  A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
  - Key Eligibilty Criteria:
    Inclusion:
    1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
    a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
    b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
    - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
    - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
    - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
    - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
    - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
    - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
    c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
    2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
    3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
    4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
    5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
- VICCURO24518
  Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
  - Key Eligibility Criteria:
    Inclusion Criteria:
    1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
    2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
    a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
    b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
    c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
    d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
    3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
    a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
    4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
    
    Exclusion Criteria:
    1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
    2. For Cohort B5 only, individuals with known uncontrolled diabetes.
    3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
    4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
    
    For pre-screening, please contact: Individual disease research teams.

Bladder - Non-Metastatic

Muscle Invasive
- Neoadjuvant
  - Cisplatin ineligible or refused
  - Cisplatin Eligible
- Adjuvant Therapy
  - ALLUROA032103
    Ph 2/3 and Ph 3 Trial of MRD-Based Optimization of Adjuvant Tx in Urothelial Cancer
    - Key Eligibility Criteria:
      Inclusion:
      1. Histologically confirmed urothelial cancer of the bladder.
      2. Radical cystectomy ≥ 3 weeks, but ≤ 12 weeks prior to pre-registration. Radical cystectomy ≤ 18 weeks prior to registration.
      3. No evidence of residual cancer or metastases after surgery (imaging required prior to registration)
      4. Available tumor tissue for “central” Signatera testing to be submitted after pre-registration. Must have evaluable ctDNA Signatera assay result [i.e., ctDNA(+) or ctDNA(-)] based on test performed as part of “central testing” after pre-registration to A032103.
      a. Cisplatin-ineligible (or cisplatin-declining) patients with a pT2N0 urothelial cancer on cystectomy who were pre-registered based on routine standard care ctDNA(+) Signatera testing must have confirmed ctDNA(+) Signatera testing on central testing. If central Signatera testing yields a ctDNA(-) result, these patients are ineligible. NOTE: This is a distinct consideration from patients with ypT2-4 and/or ypN+ urothelial cancer (i.e., patients who had received neoadjuvant cisplatin-based chemotherapy) who are eligible with either ctDNA(+) or ctDNA(-) central Signatera testing.
      5. All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic metastatic disease, within 60 days prior to registration. Patients with equivocal nodes less than 15 mm in short axis, or < 10 mm in long axis for non-lymph node lesions, not considered by the investigator to represent malignant disease will be eligible. Attempts should be made to resolve the etiology of equivocal lesions with complementary imaging (e.g., PET scan) or biopsy.
      
      For pre-screening, please contact: Message Basket: VICC RESEARCH UROTHELIAL
  - NRGUROGU015
    NRG Phase 3 Adaptive Radiation and Chemotherapy for Muscle Invasive Bladder Cancer
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Histologically proven, cT2-T3,N0M0 urothelial carcinoma of the bladder prior to randomization.
      a. Note: Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible.
      2. Must undergo a transurethral resection of bladder tumor (TURBT) prior to randomization. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection
      3. Must undergo radiological staging prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI (with or without contrast is acceptable). Patients must not have evidence of T4 or node positive disease. Fludeoxyglucose (FDG) PET Imaging is acceptable for radiological staging
      4. No diffuse carcinoma in situ (CIS) based on cystoscopy and biopsy
      5. No definitive clinical or radiologic evidence of metastatic disease
      6. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within 24 months prior to registration except Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy
      7. For patients who have completed neoadjuvant therapy, they are eligible if the pre-neoadjuvant therapy diagnosis (TURBT path) is within 180 days before randomization
      8. Must not have had prior pelvic radiation
      9. Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meet criteria specified
      
      For pre-screening, please contact: Individual disease research teams.
Non-Muscle Invasive
- SWOGGIS2012
  Platinum/Etoposide w or w/o Atezolizumab in Pts w/Poorly Diff Extrapulmonary Small Cell NEC
  - Inclusion Criteria:
    1. Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC).
    2. Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator.
    3. Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinumbased therapy +/- radiation +/- surgery provided that all therapy was completed >/= 6 months prior to registration.
    4. Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >/= 24 weeks prior to registration and participants have recovered from all prior toxicities to </= grade 1.
    5. Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least
    12 months prior to study registration.

Testicular

Biomarker
Newly Diagnosed Germ Cell Tumors
- COGAGCT1531
  PH3,Survelnce for Low Risk, Rand of Carbo vs. Cispltn for StnrdRisk Peds and Adults w/ Germ Cell
  - Key Eligibility
    Newly diagnosed AJCC Stage I, II, III testicular NSGCT
    1. Observation Only Arm: AJCC Stage IA, IB, IS, Age less than 50 years old
    Monthly tumor marker assessment x 1 year, q2 months for year 2, then q6 months for years 3 and 4.
    CXR and abdomen/pelvis CT scan are required at 3 and 12 months.
    2. Standard Risk 2 Arm: AJCC Stage II, II, and IGCCC Good Risk, age less than 25 years old.
    Patients are randomized between receiving 3 cycles of BEP or BEC
    Cycles are 21 days with visits on Day 1-5, 8 and 15. Next cycle begins on Day 22 or when eligibility
    criteria are met .
    
    Ovarian Germ Cell Tumors
    1. Low risk stratum
    No age limit
    Newly diagnosed stage I, grade 2 or 3 immature teratoma
    2. Standard risk 2 stratum
    Age > 11 and < 25
    Stage II-IV GCT containing yolk sac tumor and/or embryonal carcinoma and/or choriocarcinoma
    3. Visit Summary:
    Low risk stratum: Observation with tumor markers q 2 mos first year, q 3 months 2nd year, annually 3rd year, then as clinically
    indicated. Imaging at 4 and 12 months in first year, then as clinically indicated.
    Standard risk 1 stratum: 4 cycles of chemotherapy q 3 weeks
    Standard risk 2 stratum: 3 cycles of chemotherapy q 4 weeks
- COGAGCT1532
  Randomized Ph 3 Trial Accelerated versus Stnd BEP in Intermed. and Poor-Risk Metastatic GCT
  - Key Eligibility
    1. Newly diagnosed testicular germ cell tumor less than 45 with IGCCC Intermediate or Poor risk
    2. Patients are randomized between standard BEP and accelerated BEP (cisplatin and etoposide given every 2 weeks (days 1-5) x 4 14 day cycles, followed by weekly bleomycin x 4 (21 day cycle )).
Relapsed Refractory Germ Cell Tumors

Penile Cancer

Supportive Care

COGALTE2131
Phase 3 Triptorelin and Ovarian Reserve in Adolescents and Young Adults with Cancer
- Key Eligibility Criteria:
  
  Inclusion:
  1. < 40 years of age at the time of enrollment
  2. Patient must be a post-menarchal female and report that their initial menstrual period occurred > 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)
  3. Newly diagnosed with first cancer, exclusive of breast cancer.
  4. Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.
  5. For patients < 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m^2 cumulative cyclophosphamide equivalent dose (CED). For patients ≥ 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.
  
  Exclusion:
  1. Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
  2. Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
  3. Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
  4. Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted prior to study enrollment.
  5. Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).
  
  For pre-screening, please contact: Please reach out to the Disease specific research teams.
VICCSUPP25037
IMPACT: Improving Peripheral Neuropathy Induced by Chemotherapy with Advanced Compression Technology
- Key Eligibility Criteria:
  
  Inclusion Criteria:
  1. Planned intravenous treatment with a minimum of 12 weeks of neurotoxic chemotherapy treatment and with no planned treatment pause for surgery during neurotoxic chemotherapy treatment.
  a. With one of the following treatments:
  i. Chemotherapy regimens based on Oxaliplatin
  1. FOLFOX every 2 weeks
  2. FOLFIRINOX every 2 weeks
  ii. Chemotherapy regimens based on single-agent Paclitaxel
  1. Paclitaxel weekly
  2. Paclitaxel every 3 weeks
  iii. Chemotherapy regimens based on Paclitaxel + Carboplatin
  1. Paclitaxel weekly with Carboplatin weekly/every 3 weeks
  2. Paclitaxel every 3 weeks with Carboplatin every 3 weeks
  b. Concurrent administration of the chemotherapies listed in the inclusion criteria with or without targeted agents/immunotherapy at standard doses is allowed (such as trastuzumab, pertuzumab, bevacizumab, pembrolizumab or other immune checkpoint inhibitors).
  2. Planned taxane or platinum containing portion of chemotherapy regimen prescribed to last at least 12 weeks in duration and less than or equal to 12 months in duration. Note: The regimen is prescribed as per physician discretion in accordance with standard of care guidelines.
  
  Exclusion Criteria:
  1. Baseline peripheral neuropathy of any kind as defined by NCI CTCAE v5.0 grade > 0.
  2. Any open wounds, sores, cysts or injury on the participant's hand or on part of the upper arm where the device will be applied or on the participant's feet or part of the lower leg where the device will be applied, which in the opinion of the investigator will not be healed prior to infusion commencing or who in the opinion of the investigator will be inappropriate for inclusion in this study.
  3. Weight greater than 140 kg at the time of enrollment.
  4. Participants who are receiving neuropathy directed systemic therapies at the time of enrollment, namely, Pregabalin, Gabapentin, Amitriptyline, Nortriptyline, Venlafaxine, Duloxetine.
  
  For pre-screening, please contact: Reach out to the disease specific research team.