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

Study Overview
=================
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.

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

Conditions
-----------------
Non-colorectal Cancer, Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: HuC242-DM4


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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

| Outcome Measure | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified adult solid tumor, protocol specific, stage II pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer, recurrent pancreatic cancer