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

Sponsored by:	ImmunoGen, Inc.
Information provided by:	ImmunoGen, Inc.
ClinicalTrials.gov Identifier:	NCT00352131

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 I

MedlinePlus related topics: Cancer Pancreatic Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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

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
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

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

Locations

United States, Texas
UT Health Science Center	Recruiting
San Antonio, Texas, United States, 78245-3217
Contact: Clinical Trials Office - Institute for Drug Development 800-340-2872
Principal Investigator: Alan Mita, MD
South Texas Accelerated Research Therapeutics	Recruiting
San Antonio, Texas, United States, 78229
Contact: Anthony W. Tolcher, MD 210-593-5250

Sponsors and Collaborators

ImmunoGen, Inc.

Investigators

Study Chair:

Alain Mita, MD

Institute for Drug Development

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	ImmunoGen, Inc. ( Clinical Operations )
Study ID Numbers:	CDR0000491224, IMMUNO-101, IMMUNO-045-5011-228, UTHSC-IDD-0504
Study First Received:	July 13, 2006
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00352131 History of Changes
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

Study placed in the following topic categories:

Antibodies, Monoclonal
Antibodies
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases

Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Recurrence
Immunoglobulins
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms
Digestive System Diseases
Neoplasms by Site
Digestive System Neoplasms

Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009