Monoclonal Antibody Plus Chemotherapy in Treating Patients With Advanced Colorectal Cancer That Overexpresses HER2

NCT ID: NCT00003995

Last Updated: 2013-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-09-30

Brief Summary

Phase II trial to study the effectiveness of the monoclonal antibody trastuzumab and chemotherapy with irinotecan in treating patients who have stage IV colorectal cancer that overexpresses HER2. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Determine the objective response rate of irinotecan and trastuzumab in patients with stage IV colorectal cancer and p185 HER2 overexpression.

II. Evaluate the safety and toxic effects of this treatment regimen in these patients.

III. Determine the overall survival and time to progression in these patients in response to this treatment regimen.

IV. Determine the pharmacokinetics of trastuzumab in combination with irinotecan and antibodies to trastuzumab in these patients.

V. Determine the expression of HER2/neu in these patients.

OUTLINE: This is a multicenter study.

Patients receive a loading dose of trastuzumab IV over 90 minutes on week 1, and over 30-90 minutes weekly thereafter. Patients receive irinotecan IV over 90 minutes following trastuzumab weekly for 4 weeks. Courses are repeated every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive a loading dose of trastuzumab IV over 90 minutes on week 1, and over 30-90 minutes weekly thereafter. Patients receive irinotecan IV over 90 minutes following trastuzumab weekly for 4 weeks. Courses are repeated every 6 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

irinotecan hydrochloride

Intervention Type: DRUG

Interventions

trastuzumab

Intervention Type: BIOLOGICAL

irinotecan hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV colorectal cancer with p185 HER2 overexpression
• Bidimensionally measurable disease Indicator lesion must be outside of irradiated field No symptomatic CNS brain metastases

PATIENT CHARACTERISTICS:

• Performance status: ECOG 0-2
• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 3.0 times ULN
• Creatinine no greater than 2.0 mg/dL
• LVEF at least 45% by MUGA or ECHO
• No myocardial infarction within the past 6 months
• No congestive heart failure
• No unstable angina
• No clinically significant pericardial effusion or arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study
• No other prior malignancy within the past 5 years, except:

• Curatively treated basal or squamous cell skin cancer
• Curatively treated carcinoma in situ of the cervix
• No active serious infection or serious underlying medical condition that would prevent compliance
• No dementia or significantly altered mental status

PRIOR CONCURRENT THERAPY:

• Concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa allowed
• No prior trastuzumab
• No more than 1 prior chemotherapy regimen for advanced disease (if progressed during or within 6 months of adjuvant therapy considered to have had 1 regimen for advanced disease)
• No prior irinotecan
• Concurrent contraception, estrogen replacement therapy, or megestrol acetate for anorexia allowed
• Greater than 3 weeks since prior radiotherapy and recovered
• Greater than 3 weeks since major surgery (except simple biopsy or venous access placement) and recovered
• At least 3 weeks since prior investigational nonneoplastic drugs

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramesh K. Ramanathan, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Lifespan: The Miriam Hospital

Providence, Rhode Island, United States

Sarah Cannon-Minnie Pearl Cancer Center

Nashville, Tennessee, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Ramanathan RK, Hwang JJ, Zamboni WC, Sinicrope FA, Safran H, Wong MK, Earle M, Brufsky A, Evans T, Troetschel M, Walko C, Day R, Chen HX, Finkelstein S. Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trial. Cancer Invest. 2004;22(6):858-65. doi: 10.1081/cnv-200039645.

Reference Type: RESULT

PMID: 15641483 (View on PubMed)

Other Identifiers

PCI-98-056

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0078

Identifier Type: -

Identifier Source: secondary_id

CDR0000067205

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02307

Identifier Type: -

Identifier Source: org_study_id