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Clinical Trial COGACNS0821

Title

ACNS0821 - Temozolomide with Irinotecan versus Temozolomide, Irinotecan plus Bevacizumab (NSC# 704865, BB-IND# 7921) for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, A COG Randomized Phase II Screening Trial

Principal Investigator(s)

Adam Esbenshade

Details

  • Protocol No. COGACNS0821
  • Open Date: 10/08/2011
  • Staging: Phase II
  • Age Group: Children
  • Scope: National
  • Objective: To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan and bevacizumab for recurrent medulloblastoma (MB)/PNET of childhood.
  • Disease Sites: Neuro-Oncology; Pediatrics
  • Therapies: Chemotherapy - cytotoxic; Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: Avastin; Bevacizumab; Camptosar (Irinotecan); TMZ; Temodar; Temozolomide
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01217437
  • Secondary Protocol No: ACNS0821

Description

None Provided.

Eligibility

Ages Eligible for Study:N/A to 21 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No

Criteria

Inclusion Criteria:
• Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
• Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence
• Patients must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI); diffuse leptomeningeal disease is not considered measurable
• All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment
• Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age)
• Patients must have a life expectancy of >= 8 weeks
• Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies
• External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
• Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry
• Study specific limitations on prior therapy:
• Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor
• Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry
• Patients must have recovered from any surgical procedure before enrolling on this study:
• Patients with a major surgical procedure within 28 days prior to enrollment should be excluded
• Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded
• For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed
• There should be no anticipation of need for major surgical procedures during the course of the study
• Examples of major, intermediate, or minor surgical procedures:
• Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy
• Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy
• Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis
• Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy
• Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication
• Concomitant medications restrictions:
• Growth factor(s): Must not have received within 7 days of entry onto this study
• Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days
• Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days)
• Platelet count >= 100,000/uL (transfusion independent)
• Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows:
• =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
• =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
• =< 0.6 mg/dL (for patients aged 1 to < 2 years)
• =< 0.8 mg/dL (for patients aged 2 to < 6 years)
• =< 1 mg/dL (for patients aged 6 to < 10 years)
• =< 1.2 mg/dL (for patients aged 10 to < 13 years)
• =< 1.4 mg/dL (for female patients aged >= 13 years)
• =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
• =< 1.7 mg/dL (for male patients aged >= 16 years)
• Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age
• Central nervous system function defined as
• Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
• Adequate coagulation defined as
• International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal
Exclusion Criteria:
• Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
• Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry
• Patients must not have a known bleeding diathesis or coagulopathy
• Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry
• Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history
• Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
• Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
• Patients must not have serious and inadequately controlled cardiac arrhythmia
• Female patients who are pregnant are not eligible for this study
• Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
• Female patients of childbearing potential must have a negative pregnancy test
• Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies