Celecoxib, Leucovorin, Fluorouracil, and Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining celecoxib with leucovorin, fluorouracil, and oxaliplatin in treating patients who have metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with metastatic colorectal cancer treated with celecoxib, leucovorin calcium, fluorouracil, and oxaliplatin. Secondary Determine the toxicity of this regimen in these patients. Determine the time of disease control to evaluate progression-free survival in patients treated with this regimen. Determine the salvage surgery rate in patients treated with this regimen. Determine the duration of chemotherapy-free intervals in patients treated with this regimen. Determine the tolerability of this regimen in these patients. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive FOLFOX7 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Patients also receive oral celecoxib twice daily beginning on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease stop treatment. If disease progression occurs during the chemotherapy-free interval, patients receive an additional 6 courses. Patients with responding disease after receiving at least 6 courses of chemotherapy may undergo surgery. Beginning within 10 weeks after surgery, patients receive simplified LV5FU2 chemotherapy comprising leucovorin calcium IV over 2 hours on day 1, fluorouracil IV over 46 hours beginning on day 1, and oral celecoxib twice daily beginning on day 1. Treatment repeats every 14 days for at least 12 courses. Quality of life is assessed at baseline, during courses 4 and 6, and then every 2 months thereafter. Patients are followed at 1 month and then every 2 months thereafter. PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

Official Title
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A Phase II Of An Optimized LV-5FU-Oxaliplatin Strategy With Celebrex In Metastatic Colorectal Cancer, Optimox2-Celecoxib Study

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Metastatic disease Inoperable disease (i.e., not suitable for complete carcinological surgical resection) Measurable disease or nonmeasurable disease At least 1 unidimensionally measurable lesion at least 20 mm by conventional CT scan OR 10 mm by spiral CT scan Nonmeasurable disease defined as all other lesions, including small lesions or truly nonmeasurable disease No CNS metastases No exclusive bone metastases No symptomatic ascites or pleural effusion not evacuated before study entry PATIENT CHARACTERISTICS: Age 18 to 75 Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No known significant bleeding disorder Hepatic Alkaline phosphatase less than 3 times upper limit of normal (ULN) Renal Creatinine less than 1.5 times ULN OR Creatinine clearance at least 30 mL/min No uncontrolled hypercalcemia Cardiovascular No congestive heart failure Gastrointestinal No total or partial bowel obstruction No active gastric or duodenal ulceration or gastrointestinal bleeding within the past year No active inflammatory bowel disease Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative No peripheral sensory neuropathy No known sensitivity to celecoxib, other COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides No AIDS-related illness No active infection No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for metastatic disease Chemotherapy Prior adjuvant chemotherapy allowed provided the progression-free interval after completion of therapy is more than 6 months in duration No prior chemotherapy for metastatic disease No prior adjuvant oxaliplatin No other concurrent chemotherapy Endocrine therapy No concurrent chronic oral or IV corticosteroid use (i.e., 2 weeks or longer in duration) Radiotherapy No concurrent radiotherapy Surgery Not specified Other More than 30 days since prior investigational drugs No other concurrent investigational drugs or treatments No concurrent prophylactic fluconazole No concurrent chronic full-dose aspirin (at least 325 mg/day), other nonsteroidal anti-inflammatory drugs (NSAIDs), or other cyclooxygenase (COX)-2 inhibitors Concurrent low-dose (cardioprotective) aspirin (80 mg/day or equivalent) allowed No concurrent lithium No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: celecoxib|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  |  | 
| Time of disease control (progression-free survival) |  |  | 
| Salvage surgery rate |  |  | 
| Duration of chemotherapy-free intervals |  |  | 
| Tolerability |  |  | 
| Quality of life |  |  | 

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