BB-10901 in Treating Patients With Relapsed or Refractory Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as BB-10901, 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. PURPOSE: This phase I trial is studying the side effects and best dose of BB-10901 in treating patients with relapsed or refractory solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the safety and tolerability of BB-10901 Determine the maximum tolerated dose of this drug in these patients. Secondary Determine the pharmacokinetics of this drug in these patients. Determine the efficacy of this drug in these patients. OUTLINE: This is an open-label, multicenter, dose-escalation study. Patients receive BB-10901 IV over 40 minutes once daily on days 1-3.* Treatment repeats every 21 days NOTE: *Patients who do not tolerate 3 consecutive daily infusions of BB-10901 may receive infusions of BB-10901 on 3 alternate days, upon approval by the investigator and/or the independent Safety Review Board. Cohorts of 4-6 patients receive escalating doses of BB-10901 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4-6 patients experience dose-limiting toxicity in course 1. Up to 40 patients are treated at the MTD. After completion of study treatment, patients are followed for short term and long term follow up and survival. PROJECTED ACCRUAL: Approximately 100 patients will be accrued to this study.

Official Title
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A Phase I, Open-Label, Dose Escalation Study of Daily Dosing With BB-10901

Conditions
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Ovarian Cancer, Merkel Cell Carcinoma, SCLC

Intervention / Treatment
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* Drug: BB-10901


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS During Dose Escalation: Histologically or cytologically confirmed diagnosis of 1 of the following: Small cell lung cancer (SCLC) Other pulmonary tumors of neuroendocrine origin, including neuroendocrine carcinoma or non-SCLC with neuroendocrine features Non-pulmonary small cell carcinoma Metastatic carcinoid tumor Other CD56-positive solid tumor Diagnoses other than SCLC must have confirmation of tumor CD56 expression before study entry Relapsed or refractory disease Must have received at least 1 but no more than 3 prior chemotherapy regimens* and recovered from any acute toxicities No prior chemotherapy for carcinoid or neuroendocrine tumors DISEASE CHARACTERISTICS During MTD Expansion: Relapsed or refractory Small cell lung cancer (SCLC) Metastatic Merkel Cell carcinomas Ovarian carcinomas At the MTD: SCLC patients must have received one, but no more than 1 prior chemotherapy regimen Merkel and Ovarian patients must have received at least one prior chemotherapy regimen. Ovarian patients must have received at least one platinum-based regimen. Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan No uncontrolled carcinoid syndrome (e.g., flushing, uncontrolled diarrhea, labile blood pressure) No active brain metastases; no evidence of active disease and no requirement for anticonvulsant medications or steroids. PATIENT CHARACTERISTICS: Life expectancy ≥ 3 months ECOG performance status 0-2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Creatinine ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Bilirubin ≤ 3 times ULN No rapidly rising liver function tests (LFTs) Pancreatic function, amylase and lipase within upper limit of normal. No significant residual neurological or cardiac toxicity ≥ grade 2 after prior chemotherapy No myocardial infarction within the past 6 months No unstable angina pectoris No uncontrolled congestive heart failure No uncontrolled arrhythmia No severe aortic stenosis No history of multiple sclerosis or other demyelinating disease No Eaton-Lambert syndrome (para-neoplastic syndrome) No history of hemorrhagic stroke No CNS injury with residual neurologic deficit No ischemic stroke within the past 6 months No history of pancreatitis No current active infection or history of recurrent infection with varicella-zoster virus (shingles) or cytomegalovirus No other concurrent serious infection No chronic alcoholism No other concurrent illness or condition that would interfere with study outcome No other malignancy within the past 3 years except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix No known recent biochemical or clinical evidence of pancreatitis or extensive metastatic disease involving the pancreas PRIOR CONCURRENT THERAPY: See Disease Characteristics Total cumulative dosage of prior anthracycline treatment must not exceed threshold for cardiotoxicity No known hypersensitivity to previous monoclonal antibody therapy More than 4 weeks since prior and no concurrent chemotherapy or radiotherapy More than 4 weeks since prior and no other concurrent investigational agents At least 4 weeks since prior and no concurrent surgery No other concurrent antineoplastic treatment, including immunotherapy or steroid therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BB-10901|dose escalation study, dose will vary per cohort. patients will receive an IV infusion once every three weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessed by toxicity evaluation and prothrombin time assessments |  | these tests will be conducted at various timepoints during a patients participation in the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics assessed by measuring intact conjugate and total huN901 antibody concentration for each time point and dose level |  | PK is assessed during the first cycle (21 days) of a patients participation | 
| Efficacy assessed by measuring response (complete or partial response) and biomarker levels of neuron-specific enolase and soluble neural cell adhesion molecules (NCAM) |  | efficacy is assessed every 2 cycles during a patients participation while other blood tests are taken during every cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent small cell lung cancer, merkel cell carcinoma, ovarian cancer