Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Clinical trial to study the effectiveness of combination chemotherapy in treating patients who have advanced colorectal cancer.

Detailed Description
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OBJECTIVES: Provide oxaliplatin in combination with fluorouracil and leucovorin calcium using the FOLFOX4 regimen for front-line treatment in patients with no prior chemotherapy for advanced colorectal cancer who are not eligible for entry into ongoing clinical trials of higher priority. (The regimen in this Treatment Referral Center protocol is one that was found to be superior in a recent national intergroup study.) Further determine the safety of this regimen in these patients. Further determine the anti-tumor activity of this regimen, defined as the rate of time-to-treatment failure, time to progression, and survival, in these patients. Capture data on subsequent salvage therapy administered to patients treated with this protocol. OUTLINE: This is an open-label, multicenter study. Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with clinical evidence of benefit from this treatment, defined as stable disease, partial response, or complete response as well as no increase in size of any measurable or evaluable lesion and no new sites of disease, may be eligible for additional courses. Patients are followed until death. PROJECTED ACCRUAL: A maximum of 300 patients per month will be accrued for this study.

Official Title
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Oxaliplatin (NSC 266046) in Combination With 5-Fluorouracil and Leucovorin (FOLFOX4) for Patients Who Have Not Received Prior Chemotherapy for Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Must not be eligible for Inter-group, Cooperative Group, or local clinical trials of higher priority Histologically or cytologically confirmed colorectal adenocarcinoma Locally advanced or metastatic Not curable by surgery or amenable to radiation therapy with curative intent Site of primary lesion must be or have been in the large bowel, as confirmed endoscopically, radiologically, or surgically No separate histological or cytological confirmation of metastatic disease is required for patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer unless: More than 5 years has elapsed since prior primary surgery and the development of metastatic disease OR Primary cancer was a Duke's A or B1 lesion Measurable or evaluable disease No prior chemotherapy for advanced colorectal cancer Prior adjuvant therapy allowed for resected stage II, III, or IV disease with any regimen containing fluorouracil with or without irinotecan or with immunotherapy, provided recurrent disease has been documented PATIENT CHARACTERISTICS: Age: 15 and over Performance status: ECOG 0-2 OR Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL (transfusion allowed) Hepatic: Bilirubin no greater than 1.5 mg/dL (regardless of liver involvement secondary to tumor) AST less than 5 times upper limit of normal (ULN) Alkaline phosphatase less than 5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No uncontrolled high blood pressure No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No myocardial infarction within the past 6 months No New York Heart Association class III-IV cardiac disease Pulmonary: No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung No pleural effusion or ascites that causes respiratory compromise (i.e., dyspnea grade 2 or greater) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reactions to compounds of similar chemical or biologic composition to platinum agents or oxaliplatin as well as other study agents No neuropathy grade 2 or greater, regardless of causality No HIV-positive patients receiving combination anti-retroviral therapy No ongoing or active infection No uncontrolled concurrent illness No psychiatric or social situations that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent sargramostim Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy) Surgery: See Disease Characteristics At least 4 weeks since prior major surgery (e.g., laparotomy) At least 2 weeks since prior minor surgery Insertion of a vascular access device is not considered major or minor surgery Other: Recovered from effects of prior treatment No other concurrent investigational agents No oral cryotherapy on day 1 of each course

Ages Eligible for Study
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Minimum Age: 15 Years

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFOX regimen|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

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 III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer