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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; SCLC; Merkel Cell Carcinoma
• Intervention / Treatment: Drug: BB-10901

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Manchester, England, United Kingdom, M20 9BX
      • Christie Hospital NHS Trust
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Cancer Research Centre at Weston Park Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust - Surrey
• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute
  • Ohio
    • Columbus, Ohio, United States
      • The Ohio State University Cancer Center and Research Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: ImmunoGen, Inc.
• Investigators: Study Chair: Paul C. Lorigan, MD, The Christie NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: June 28, 2006
• First Submitted That Met QC Criteria: June 28, 2006
• First Posted (Estimate): June 29, 2006

Study Record Updates

• Last Update Posted (Estimate): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: recurrent small cell lung cancer; ovarian cancer; merkel cell carcinoma
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Ovarian Neoplasms; Carcinoma, Merkel Cell; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Lorvotuzumab mertansine
• Other Study ID Numbers: CDR0000491231; IMMUNO-C10/IVB/002; IMGN-002; MDA-2004-0557