Maytansinoid DM4-Conjugated Humanized Monoclonal Antibody HuC242 In Treating Patients With Solid Tumors

Study Overview

Maytansinoid DM4-Conjugated Humanized Monoclonal Antibody huC242 in Treating Patients 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.

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.

Non-colorectal Cancer
Pancreatic Cancer

DRUG: HuC242-DM4

CDR0000491224
IMMUNO-101
IMMUNO-045-5011-228
UTHSC-IDD-0504

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-07-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2010-03-16
First Submitted that Met QC Criteria 2006-07-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2010-03-17
First Posted (ESTIMATED) 2006-07-14	Results First Posted N/A	Last Verified 2010-03

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Dose-limiting toxicity		for the duration of the trial
Maximum tolerated dose		for the duration of the trial

Secondary Outcome Measures	Measure Description	Time Frame
Toxicity		for the duration of the trial
Pharmacokinetics		for the duration of the trial
Antitumor activity		for the duration of the trial

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

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

Investigators

STUDY_CHAIR: Alain Mita, MD, Institute for Drug Development

Publications

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.

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Patients

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Clinical Trial Record