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

This study has been completed.
Sponsor:
Information provided by:
ImmunoGen, Inc.
ClinicalTrials.gov Identifier:
NCT00352131
First received: July 13, 2006
Last updated: March 16, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Non-colorectal Cancer
Pancreatic Cancer
Drug: HuC242-DM4
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by ImmunoGen, Inc.:

Primary Outcome Measures:
  • Dose-limiting toxicity [ Time Frame: for the duration of the trial ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Time Frame: for the duration of the trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: for the duration of the trial ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Time Frame: for the duration of the trial ] [ Designated as safety issue: No ]
  • Antitumor activity [ Time Frame: for the duration of the trial ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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.
    Other Name: IMGN242
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352131

Locations
United States, Texas
UT Health Science Center
San Antonio, Texas, United States, 78245-3217
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
ImmunoGen, Inc.
Investigators
Study Chair: Alain Mita, MD Institute for Drug Development
  More Information

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.

Responsible Party: Clinical Operations, ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT00352131     History of Changes
Obsolete Identifiers: NCT00625716
Other Study ID Numbers: CDR0000491224, IMMUNO-101, IMMUNO-045-5011-228, UTHSC-IDD-0504
Study First Received: July 13, 2006
Last Updated: March 16, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by ImmunoGen, Inc.:
unspecified adult solid tumor, protocol specific
stage II pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014