Neuroendocrine

Gastrointestinal Cancer
Neuroendocrine
- Low/Intermediate
  - First Line
    - VICC-DTPHI23045
      Ph I/IIa Study of [212Pb]VMT-a-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 + Tumors
      - Key Eligibility Criteria:
        
        Inclusion Criteria:
        1. Adult PRRT-naïve subjects with NETs or meningioma by local pathology
        2. Disease described clinically as:
        (a) Locally advanced/unresectable or metastatic NETs for dose-finding part of the study
        (b) Locally advanced/unresectable or metastatic GEP-NETs, bronchial NETs, pheochromocytoma, or paragangliomas for the dose-expansion part of the study
        (c) Requiring at least 1 prior surgery (resection/biopsy) and a maximum of 1 line of EBRT, if technically feasible, for meningioma.
        3. For meningioma: histologically confirmed diagnosis of meningioma, i.e., all grades (1 to 3)
        4. Radiological evidence of measurable disease by: (a) For NETs: RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment.
        5. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment. (b) For meningioma: RANO meningioma criteria on contrast-enhanced skull MRI for meningioma within 3 weeks prior to enrollment.
        6. Demonstration of lesional SSTR expression:
        (a) For NETs: using an FDA-approved somatostatin receptor PET imaging agent, e.g. [68Ga]DOTATATE, [64Cu]DOTATATE, or [68Ga]DOTATOC (b) For meningioma: using a standard-of-care SSTR PET imaging agent within 45 days of enrollment
        
        Exclusion Criteria:
        1. Known hypersensitivity to SSA, SSTR imaging agents or any of the excipients of [212Pb]VMT-a-NET.
        2. Known additional malignancy that is progressing or requires active treatment.
        3. Prior treatment with systemic PRRT based therapies (i.e., [90Y] DOTATATE/DOTATOC or [177Lu] DOTATATE)
        4. Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to enrollment.
        5. For Subjects with NETs: Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrollment and the subject has been off steroid support for at least 14 days prior to enrollment.
        6. QTc > 450 milliseconds for males and females.
        
        For internal pre-screening, please contact: Epic message basket- VICC RESEARCH PHASE 1
    - VICCGI2283
      Surgical Debulking Prior to PRRT in Patients with Well Differentiated GEP NETs
      - Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
        1. Signed and dated written informed consent.
        2. Male or female ≥ 18 years of age on the day of signing informed consent.
        3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
        4. Histologically confirmed well-differentiated gastrointestinal or pancreatic neuroendocrine
        tumor that is Grade 1 or Grade 2 (Ki-67 ≤ 20%).
        5. Somatostatin receptor avidity of known or suspected neuroendocrine tumor (NET) lesion(s)
        assessed by a baseline copper-64 dotatate PET/CT scan performed within 6 months (180
        days) prior to surgical debulking on Study Day 0. The somatostatin receptor avidity of the
        majority of suspected NET lesion(s) must be ≥ normal liver uptake.
        6. Patient must have hepatic metastasis or hepatic metastases. Provided required hepatic
        metastatic disease is present, patient can also have any other site or sites of metastatic
        disease.
        7. Adequate organ and bone marrow function resulted ≤ 90 days prior to surgical debulking on
        Day 0 of participation in this study:
        • White blood cell count (WBC) ≥ 2000/µL.
        • Platelets ≥ 75,000/µL.
        • Hemoglobin ≥ 8.0 g/dL.
        • Creatinine clearance (CrCl) ≥ 30 mL/minute
        (as calculated by the Cockcroft-Gault Formula – see Appendix 2 – with estimated
        creatinine clearance rate [eCCR] ≥ 30 mL/min required for eligibility inclusion; or
        calculated/measured by an alternative established institutional standard consistently
        applied across participants at the site).
        • Total bilirubin ≤ 3.0 times institutional upper limit of normal (ULN).
        • Serum albumin ≥ 3.0 g/dL unless the prothrombin time is within normal range.
        8. Women must not be breastfeeding and further agree to not breastfeed during treatment with
        lutetium Lu 177 dotatate; and for at least 2.5 months after patient’s final dose of lutetium Lu
        177 dotatate.
        9. A woman of childbearing potential (WOCBP) – see Appendix 3 for definition of WOCBP –
        must have a negative serum or urine pregnancy test resulted within 28 days prior to initiation
        of first dose of lutetium Lu 177 dotatate on Cycle 1, Day 1; and must agree to follow
        instructions for using acceptable contraception (Appendix 3) from the time of signing consent,
        and until 7 months after her final dose of lutetium Lu 177 dotatate
    - VICCGI25020
      Phase 2/3 Study of Zanzalintinib v Everolimus in Participants w/Locally Advanced or Metastatic NETs
    - SWOGGIS2104
      Phase 2 Trial of Postoperative Adjuvant Capecitabine + Temozolimide vs Observation in HR pNETs
      - Key eligibility criteria:
        
        a. Participants must have a histologic diagnosis of well-differentiated (as defined in Section 4.1) pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 120 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease, unless liver oligo-metastatic disease was deemed to be resected/ablated at time of surgery. If longer than 90 days, updated scans are recommended for grade 3 tumors or metastatic tumors. Acceptable scans are multiphase CT abdomen, MRI with IV contrast of the abdomen; Multiphasic CT of the abdomen should include arterial-phase imaging of the liver in addition to the portal venous phase. The most recent scan should be submitted.
        b. Resection must have been an R0 or R1 per treating investigator’s assessment and/or pathology report. See Section 18.3 for definitions of R0 and R1.
        c. Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection.
        d. Participants must have Ki-67 testing performed from the surgical specimen collected between 14 and 120 days prior to registration. The Ki-67 result must be ≥ 3% and ≤ 55%.
        f. Participants must not have unresected or unablated metastatic disease.
        g. Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis.
  - VICCMD2132
    Ph2 Study of Belzutifan MonoTx in Advanced PPGL, pNET, VHL-Tumors, wt GIST, or HIF-2a Tumors
    - Drug(s)/Mechanism:
      Belzutifan
      
      Eligiblity information:
      Cohort B1 specific inclusion criteria:
      
      1. Have a diagnosis of VHL disease as determined by a germline test (documented germline VHL gene alteration) locally and/or clinical diagnosis, which can be made in the
      following instances:
      a. in a participant with a family history of VHL disease and at least one of the characteristic VHL-related tumors (eg, retinal HBs, CNS HBs, clear cell RCCs, pNETs, and endolymphatic sac tumors).
      b. in the presence of 2 or more retinal or CNS HBs.
      c. in the presence of 1 retinal or CNS HB, plus at least 1 of the characteristic VHLrelated visceral tumors, excluding renal and epididymal cysts.
      
      2. Have at least 1 measurable PPGL or pNET per RECIST 1.1 by CT or MRI as assessed by local site investigator/radiology assessment and verified by BICR. BICR must verify the
      presence of radiologically measurable disease per RECIST 1.1 for either PPGL or pNET for the participant to be eligible for the study.
      
      3. For Cohort B1 participants with PPGL:
      a. No pheochromocytoma >5 cm or paraganglioma >4 cm that requires immediate surgery.
      b. Participants should have adequately controlled BP defined as BP 150/90 mm Hg and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 2 weeks prior to start of study treatment.
      c. Metastatic or locally advanced, unresectable PPGL will be exclusionary.
      d. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).
      
      4. For Cohort B1 participants with pNET:
      a. No lesion(s) located in the head of the pancreas must be >2 cm that requires immediate surgery.
      b. No lesion(s) located in the body or tail of the pancreas must be >3 cm that requires immediate surgery.
      c. Locally advanced, unresectable or metastatic pNET will be exclusionary.
      d. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).
      
      5. For Cohort B1 participants with RCC:
      a. No lesion(s) must be >3 cm that requires immediate surgery.
      b. Metastatic RCC will be exclusionary.
      c. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).
      
      6. For Cohort D participants with advanced solid tumors with HIF-2A related genetic alterations:
      a. Local test report documenting germline or somatic mutations in at least one of the HIF-2A related genes (HIF-2A/EPAS1, FH, SDHA, SDHB, SDHC, SDHD, SDHAF2, EGLN1, EGLN2, MDH2, ELOC/TCEB1).
      b. Has locally advanced or metastatic solid tumor that is not amenable to surgery or curative intent treatment.
      c. Participants must have progressed on/after standard therapy for advanced/metastatic disease. More than 3 prior therapies will not be allowed for this cohort in the advanced/metastatic setting.
      
      For pre-screening, please contact: Message Basket: VICC RESEARCH REFERRALS/ELIGIBILITY
  - 2L
    - VICCGI25020
      Phase 2/3 Study of Zanzalintinib v Everolimus in Participants w/Locally Advanced or Metastatic NETs
- High Grade
  - 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.