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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Biological: trastuzumab; Drug: irinotecan hydrochloride	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	32 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II and Pharmacokinetic Study of CPT-11 and Trastuzumab (RhuMab HER2, Herceptin) in Advanced Colo-Rectal Cancer With p185 HER 2 Overexpression
Study Start Date :	September 1999
Actual Primary Completion Date :	March 2006

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 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.	Biological: trastuzumab Drug: irinotecan hydrochloride

Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, New York
Albert Einstein Comprehensive Cancer Center
Bronx, New York, United States, 10461
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Lifespan: The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Tennessee
Sarah Cannon-Minnie Pearl Cancer Center
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:	Ramesh K. Ramanathan, MD	University of Pittsburgh

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

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.

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003995 History of Changes
Other Study ID Numbers:	NCI-2012-02307; PCI-98-056; NCI-T98-0078; CDR0000067205 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted:	June 25, 2004
Last Update Posted:	February 8, 2013
Last Verified:	June 2007

Keywords provided by National Cancer Institute (NCI):

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases	Rectal Diseases; Irinotecan; Trastuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action