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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II and Pharmacokinetic Study of CPT-11 and Trastuzumab (RhuMab HER2, Herceptin) in Advanced Colo-Rectal Cancer With p185 HER 2 Overexpression

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br> <br> Drug: irinotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer