Oxaliplatin, Irinotecan, and Capecitabine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with oxaliplatin and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I) Determine the efficacy of this regimen in these patients. (Phase II) Secondary Determine the tolerability of this regimen in these patients. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a phase II study. Phase I: Patients receive oxaliplatin IV over 2 hours on days 1 and 15, irinotecan IV over 1 hour on days 8 and 22, and oral capecitabine twice daily on days 1-29. Treatment repeats every 5 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive capecitabine at the MTD and irinotecan and oxaliplatin as in phase I. After completion of study treatment, patients are followed every 2 months for 1 year and then every 4 months thereafter. PROJECTED ACCRUAL: A total of 23-32 patients (3-12 for the phase I portion and 20 for the phase II portion) will be accrued for this study within 2.75 years

Official Title
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Oxaliplatin, Irinotecan, and Capecitabine as a Combination Regimen for First-Line Treatment of Advanced or Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: irinotecan hydrochloride
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed unresectable advanced or metastatic colorectal cancer Measurable disease (phase II only) At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan or MRI No presence or history of CNS metastases PATIENT CHARACTERISTICS: Age 18 to 70 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.25 times upper limit of normal (ULN) (1.5 times ULN if liver metastases are present) AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present) Renal Creatinine clearance > 60 mL/min Cardiovascular No New York Heart Association class III-IV congestive heart failure No symptomatic coronary artery disease No uncontrolled cardiac arrhythmia No myocardial infarction within the past year No other clinically significant cardiac disease Immunologic No active autoimmune disease No uncontrolled infection No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluorouracil No known hypersensitivity to any component of study drugs Other Not pregnant or nursing Negative pregnancy test Patients must use effective contraception during and for 1 year after study participation No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer No peripheral neuropathy > grade 1 of any origin (e.g., alcohol or diabetes) No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication No psychiatric disability that would preclude study compliance No uncontrolled diabetes No other serious underlying medical condition that would preclude study participation No known dihydropyrimidine dehydrogenase deficiency PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent prophylactic hematopoietic growth factors Chemotherapy More than 6 months since prior adjuvant fluoropyrimidine chemotherapy No other prior chemotherapy Endocrine therapy Not specified Radiotherapy No concurrent radiotherapy Concurrent radiotherapy of a single painful lesion allowed Surgery Not specified Other More than 30 days since prior clinical trial participation No other concurrent experimental drugs No other concurrent anticancer therapy No concurrent sorivudine or its chemically-related analogues (e.g., lamivudine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Oxaliplatin, Irinotecan, and Capecitabine | Drug: Capecitabine<br>* capecitabine<br>Drug: irinotecan hydrochloride<br>* irinotecan hydrochloride<br>Drug: oxaliplatin<br>* oxaliplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| capecitabine + oxaliplatin + irinotecan dose finding | Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I) | 30 days | 
| Efficacy of Oxaliplatin, Irinotecan, and Capecitabine | Determine the efficacy of this regimen in these patients (Phase II) | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (CR or PR) as measured after completion of study treatment |  | 2 months | 
| Adverse events as measured after completion of study treatment |  | 2 months | 
| Time to progression |  | life-long | 
| Time to treatment failure as measured after completion of study treatment |  | life-long | 
| Overall survival |  | life-long | 

 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