TheranosticTrials.org

Clinical Trial · NCT00450827

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab in Treating Patients With Relapsed or Refractory Neuroblastoma

Overview

RATIONALE: Monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8 and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of neuroblastoma by blocking blood flow to the tumor. Giving iodine I 131 monoclonal antibody 3F8 together with bevacizumab may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 monoclonal antibody 3F8 when given together with bevacizumab in treating patients with relapsed or refractory neuroblastoma.

Sponsor

Memorial Sloan Kettering Cancer Center

Phase

Phase 1

Contacts

Nai-Kong V. Cheung, MD, PhD (PRINCIPAL_INVESTIGATOR)

Shakeel Modak, MD (STUDY_CHAIR)

ClinicalTrials.gov

NCT00450827

Drug / Compound

3F8

Isotope(s):
Target(s):
  • GD2
Ligand Class: Antibodies

Eligibility

Inclusion

  • Must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy.
  • Patients must have the diagnosis of NB in accordance with the International Criteria, i.e., either histopathology (confirmed by the MSKCC Department of Pathology) or BM involvement plus elevated urinary catecholamines.
  • Minimum life expectancy of four weeks.
  • Prior Therapy: At least 2 weeks should have elapsed since any biologic therapy. Three weeks should have elapsed since last dose of chemotherapy or radioimmunotherapy.
  • Stem cells: Patients must have an autologous hematopoietic stem cell product cryopreserved and available for re-infusion after MIBG treatment. The minimum dose for hematopoietic stem cells is 2 X106 CD34+ cells/kg.
  • Patients must have evaluable (microscopic marrow metastasis, MIBG or PET scans) or measurable (CT, MRI) disease.

Exclusion

  • Pulmonary or CNS metastases: pre-therapy CT or MRI of head and chest must be carried out.
  • Inability or unwillingness to comply with radiation safety procedures or protocol requirements.
  • Patients with myelosuppression are not excluded if ANC ≥ 500/uL. Platelet count should be \> 50,000/ul and hemoglobin should be \> 8gm/dl. Patients may receive platelet or red blood cell transfusions to maintain hemoglobin and platelets at clinical appropriate levels.
  • HAMA \>1000 ELISA units/ml.
  • Thrombosis: patients must not have had a deep venous or arterial thrombosis (non-central venous catheter related) within the last three months prior to study entry. Patients with cerebrovascular accident or transient ischemic attack within 6 months of therapy are excluded. Patients with history of peripheral vascular disease, myocardial infarction or unstable angina are excluded.
  • Proteinuria: Urine protein: creatinine ratio ≥ 1.0
  • Surgical procedures.
  • Patients must be least 24 hours from having after surgical procedures such as placement of central catheter.
  • History of allergy to mouse proteins, Chinese hamster ovary cells products or other recombinant human antibodies
  • Uncontrolled hypertension.
  • Patients who have undergone major surgery \<28 days prior to beginning therapy with bevacizumab are excluded.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry.
  • Patients with documented chronic non-healing wound, ulcer or bone fracture
  • Severe major organ toxicity. Renal, cardiac, hepatic, pulmonary, gastrointestinal and neurologic toxicity should all be grade 2 or less (per NCI CTC version 3 criteria). Specifically, serum creatinine should be ≤3 x upper limit of normal (ULN), serum AST and ALT ≤5 x ULN, serum bilirubin ≤ 3 x ULN, LV shortening fraction should be ≥15%.
  • Active serious infections not controlled by antibiotics.
  • Patients will be excluded if major surgery (e.g. abdominal or thoracic surgery for resection of tumor) is anticipated during the course of the study.Known bleeding diathesis or coagulopathy. Patients on anti-coagulants (except for heparin flushes for centra venous catheter maintenance) are excluded.
  • Patients \<7days from minor surgeries (e.g. fine needle or core biopsies) and/or the unhealed wounds from these procedures are excluded.