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

NCT00450827 | Completed Phase 1

• 3 other identifiers: 06-072P30CA008748MSKCC-06072
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  2 years

Study Arms (1)

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab

EXPERIMENTAL

Patients will be administered a therapeutic doses of intravenous (IV) 131I-3F8 given in a single dose per the dose escalation regimen on day 0 of study. This will be followed by blood draws for pharmacokinetic and dosimetry studies and by gamma camera scan, where feasible. Bevacizumab will be administered at a fixed dose of 15mg/kg on days 1 and 15. Thyroid protection is commenced 10 days prior to administration of 131I-3F8 and continued for 28 days after the therapeutic dose of 131I-3F8. ASCR will be carried out if ANC \< 500/ul on day 28 (blood radioactivity will be confirmed to be \<1 uCi/ml prior to ASCR). ASCR will be carried out sooner in the case of life-threatening infection in the setting of neutropenia (ANC\<500). G-CSF can be used to maintain ANC\>500/ul but should not be used for 24 hours immediately before and after ASCR. Blood product support will be provided with platelet and red cell transfusions as required.

Biological: bevacizumab; Biological: filgrastim; Procedure: autologous hematopoietic stem cell transplantation; Radiation: iodine I 131 monoclonal antibody 3F8

Interventions

bevacizumab BIOLOGICAL

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab

filgrastim BIOLOGICAL

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab

autologous hematopoietic stem cell transplantation PROCEDURE

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab

iodine I 131 monoclonal antibody 3F8 RADIATION

Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy.
• Patients must have evaluable (microscopic marrow metastasis, MIBG or PET scans) or measurable (CT, MRI) disease.
• 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.
• Age \>1 year and able to cooperate with radiation safety restrictions during therapy period.
• 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.
• Minimum life expectancy of four weeks.
• Signed informed consent indicating awareness of the investigational nature of this program.

You may not qualify if:

• 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%.
• 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.
• Patients with documented chronic non-healing wound, ulcer or bone fracture
• Surgical procedures.
• Patients who have undergone major surgery \<28 days prior to beginning therapy with bevacizumab are excluded.
• Patients must be least 24 hours from having after surgical procedures such as placement of central catheter.
• Patients \<7days from minor surgeries (e.g. fine needle or core biopsies) and/or the unhealed wounds from these procedures are excluded.
• 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.
• 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.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry.
• Pulmonary or CNS metastases: pre-therapy CT or MRI of head and chest must be carried out.
• Proteinuria: Urine protein: creatinine ratio ≥ 1.0
• Uncontrolled hypertension.
• HAMA \>1000 ELISA units/ml.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Bevacizumab; Filgrastim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Shakeel Modak, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• Nai-Kong V. Cheung, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: August 1, 2006
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 28, 2015

Record last verified: 2015-09

Locations

US (1)