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

NCT ID: NCT00352131

Last Updated: 2010-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2009-12-31

Brief Summary

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.

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.

Conditions

Non-colorectal Cancer; Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

HuC242-DM4

Dose escalation study to define maximum tolerated dose. Doses will vary per cohort. Patients will receive an IV infusion once every three weeks.

Intervention Type: DRUG

Other Intervention Names

IMGN242

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ImmunoGen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

ImmunoGen, Inc.

Principal Investigators

Alain Mita, MD

Role: STUDY_CHAIR

Institute for Drug Development

Locations

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

UT Health Science Center

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: RESULT

Other Identifiers

IMMUNO-101

Identifier Type: -

Identifier Source: secondary_id

IMMUNO-045-5011-228

Identifier Type: -

Identifier Source: secondary_id

UTHSC-IDD-0504

Identifier Type: -

Identifier Source: secondary_id

CDR0000491224

Identifier Type: -

Identifier Source: org_study_id

NCT00625716

Identifier Type: -

Identifier Source: nct_alias