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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00352131
• Other study ID #: CDR0000491224
• Secondary ID: IMMUNO-101IMMUNO
• Status: Completed
• Phase: Phase 1
• First received: July 13, 2006
• Last updated: March 16, 2010
• Start date: February 2005
• Est. completion date: December 2009

Study information

• Verified date: March 2010
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00625716

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Non-colorectal Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	UT Health Science Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity		for the duration of the trial	Yes
Primary	Maximum tolerated dose		for the duration of the trial	Yes
Secondary	Toxicity		for the duration of the trial	Yes
Secondary	Pharmacokinetics		for the duration of the trial	No
Secondary	Antitumor activity		for the duration of the trial	No