Maytansinoid DM4-Conjugated Humanized Monoclonal Antibody huC242 in Treating Patients With Solid Tumors

March 16, 2010 updated by: ImmunoGen, Inc.

A Phase I Study to Assess the Safety and Pharmacokinetics of huC242-DM4 Administered as a Single Intravenous Infusion Once Every Three Weeks to Subjects With Solid Tumors

RATIONALE: Monoclonal antibodies, such as maytansinoid DM4-conjugated humanized monoclonal antibody huC242, 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 maytansinoid DM4-conjugated humanized monoclonal antibody huC242 in treating patients with solid tumors that cannot be removed by surgery or have spread to other parts of the body.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Drug: HuC242-DM4

Detailed Description

OBJECTIVES:

Primary

Determine the dose-limiting toxicity and maximum tolerated dose of maytansinoid DM4-conjugated humanized monoclonal antibody huC242 in patients with inoperable or metastatic colorectal cancer, pancreatic cancer, or other solid tumors.

Secondary

Determine the qualitative and quantitative toxicities of this drug in these patients.
Characterize the pharmacokinetics of this drug in these patients.
Describe any antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, nonrandomized, dose-escalation study.

Patients receive maytansinoid DM4-conjugated humanized monoclonal antibody huC242 IV over 4-5 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of maytansinoid DM4-conjugated humanized monoclonal antibody huC242 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 15 patients are treated at the MTD.

Patients undergo blood collection at baseline and periodically during study for pharmacokinetic studies.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Texas
  - San Antonio, Texas, United States, 78229
    - South Texas Accelerated Research Therapeutics
  - San Antonio, Texas, United States, 78245-3217
    - UT Health Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor
- Inoperable or metastatic disease
Failed standard therapy
Confirmed cancer antigen (CanAg) expression
- Patients must have non-colorectal cancer or pancreatic cancer
- Tumor must have a homogeneous pattern (i.e., staining present in > 75% of tumor cells for CanAg) and are 2+ or 3+ intensity by immunohistochemistry * No known leptomeningeal disease or progressive brain disease

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/mm³
Hemoglobin ≥ 9 g/dL (transfusion allowed)
Platelet count ≥ 100,000/mm³
aPTT and INR ≤ 1.5 times upper limit of normal (ULN)
Creatinine ≤ 1.5 mg/dL
Creatinine clearance ≥ 60 mL/min
Bilirubin ≤ 1.5 mg/dL
AST and ALT < 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 30 days after completion of study treatment
No hypersensitivity to agents of the same class as the study drug, humanized or nonhumanized antibodies, or immunoconjugates
No active, uncontrolled infection
No hepatitis B surface antigen or hepatitis C antibody positivity
No history of alcoholic liver disease
No serious medical or psychiatric disorder that would preclude compliance with study requirements
No peripheral neuropathy > grade 1
No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage A low-grade prostate cancer
No severe concurrent disease or condition that, in the opinion of the investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C)
At least 4 weeks since prior radiotherapy, immunotherapy, or hormone therapy for cancer
At least 4 weeks since prior major surgery
No concurrent chemotherapy, other immunotherapy, radiotherapy, or other investigational therapy
- Palliative radiotherapy for related bone metastases allowed
No other concurrent anticancer therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Dose-limiting toxicity Time Frame: for the duration of the trial	for the duration of the trial
Maximum tolerated dose Time Frame: for the duration of the trial	for the duration of the trial

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity Time Frame: for the duration of the trial	for the duration of the trial
Pharmacokinetics Time Frame: for the duration of the trial	for the duration of the trial
Antitumor activity Time Frame: for the duration of the trial	for the duration of the trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ImmunoGen, Inc.

Investigators

Study Chair: Alain Mita, MD, Institute for Drug Development

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Sankhala KK, Mita AC, Ricart AD, et al.: A phase I and pharmacokinetic study of a CanAg-targeted immunoconjugate, HuC242-DM4, in patients with CanAg-expressing solid tumors. [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-B70, 2007.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)