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

ImmunoGen

Status and phase

Completed

Phase 1

Conditions

Non-colorectal Cancer

Pancreatic Cancer

Treatments

Drug: HuC242-DM4

Study type

Interventional

Funder types

Industry

Identifiers

NCT00352131

CDR0000491224

UTHSC-IDD-0504

IMMUNO-045-5011-228

IMMUNO-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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