Gemcitabine, Capecitabine, and Oxaliplatin as Second-Line Therapy in Treating Patients With Advanced Colorectal Cancer Previously Treated With Irinotecan

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, capecitabine, and oxaliplatin, 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 gemcitabine when given together with capecitabine and oxaliplatin as second-line therapy and to see how well it works in treating patients with advanced colorectal cancer previously treated with irinotecan.

Detailed Description
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OBJECTIVES: Primary Define the dose-limiting toxicity and maximum tolerated dose of gemcitabine hydrochloride when administered with capecitabine and oxaliplatin as second-line therapy in patients with advanced colorectal cancer previously treated with irinotecan hydrochloride. (Phase I) Determine the recommended phase II dose of gemcitabine hydrochloride in these patients. (Phase I) Assess overall response rate in patients treated with this regimen. (Phase II) Secondary Assess the progression-free survival of patients treated with this regimen. (Phase II) Assess the time to treatment failure, duration of response, and time to response in patients treated with this regimen. (Phase II) Assess the overall survival of patients treated with this regimen. (Phase II) Assess the safety of this regimen in these patients. (Phase II) OUTLINE: This is a multicenter, phase I, dose-escalation study of gemcitabine hydrochloride, followed by a phase II, open-label study. Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, oral capecitabine twice daily on days 1-14, and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. Phase II: Patients receive gemcitabine hydrochloride at the MTD determined in phase I and capecitabine and oxaliplatin as in phase I.

Official Title
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A Phase I/II Study to Determine the Safety and Efficacy of Second-Line Treatment With XELOX Plus Gemcitabine in Irinotecan Pre-Treated Advanced Colorectal Cancer Patients

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced colorectal adenocarcinoma Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Must have received prior irinotecan hydrochloride with a progression-free interval of < 3 months No symptomatic brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Total bilirubin ≤ 2 times upper limit of normal (ULN) AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present) Creatinine ≤ 1.5 times ULN No significant cardiac abnormalities by ECG No known hypersensitivity to the study drugs or any of their components No myocardial infarction within the past 12 months No uncontrolled congestive heart failure No cardiovascular disorder ≥ grade 3 despite treatment No other malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix No significant disease, that in the opinion of the investigator, would preclude study treatment (e.g., active infections, interstitial lung disease, or peripheral neuropathy) No history of significant neurological or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder) No legal incapacity or limited legal capacity that would preclude study participation PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy More than 30 days since prior participation in another clinical trial No concurrent warfarin, phenprocoumon, phenytoin, or sorivudine

Ages Eligible for Study
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Minimum Age: 18 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: capecitabine|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate as assessed by RECIST criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Duration of response |  |  | 
| Time to treatment failure |  |  | 
| Overall survival |  |  | 
| Time to response |  |  | 

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