Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: This phase II trial is studying combination chemotherapy plus trastuzumab to see how well it works in treating patients with advanced, recurrent, or metastatic colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the response rate of patients who overexpress HER-2/neu with metastatic colorectal adenocarcinoma who have progressed on at least 1 prior, but no more than 2 prior, chemotherapy regimens for metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and trastuzumab (Herceptin). Determine the time to progression of these patients treated with this regimen. Determine the overall toxicity of this regimen in these patients. OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and 15. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression. PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

Official Title
-----------------
Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin, Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Biological: trastuzumab
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed advanced, recurrent, or metastatic colorectal adenocarcinoma Resected CNS metastases stable greater than 1 month after completion of radiotherapy for CNS metastases eligible No existing CNS metastases allowed Measurable disease At least 1 dimension as at least 20 mm with conventional techniques OR At least 10 mm with spiral CT scan No truly nonmeasurable lesions: Bone lesions Leptomeningeal disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or irinotecan containing treatment regimens for metastatic colorectal cancer Must have documented HER-2/neu overexpression by immunohistochemistry staining Staining score at least 2+ PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL AST no greater than 2.5 times upper limit of normal Renal: Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular: No history of cardiac ischemia or congestive heart failure LVEF at least 50% by ECG or MUGA Other: Not pregnant or nursing Fertile patients must use effective contraception No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in situ of the cervix unless completed therapy and considered to be at less than 30% risk of relapse PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior platinum containing chemotherapy At least 3 weeks since prior chemotherapy and recovered No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy and recovered Surgery: Not specified

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Chemotx<br>Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy | Biological: trastuzumab<br>* 4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22)<br>* Other names: Herceptin;Drug: fluorouracil<br>* 500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break<br>* Other names: 5-FU;Drug: leucovorin calcium<br>* 500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break<br>Drug: oxaliplatin<br>* 85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Every 2 tx cycles | 
| Time to progression |  | Every 2 tx cycles | 
| Overall toxicity |  | Each cycle during tx | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum