Phase I Study of Capecitabine in Combination With Cisplatin and Irinotecan

Study Overview
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Brief Summary
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To determine the safety and feasibility of administering Capecitabine with the combination of Cisplatin and Irinotecan. To determine the Phase II recommended dose and toxicity profile of Capecitabine with the combination of Cisplatin and Irinotecan. To study the biologic effect of pyrimidine inhibition on DNA repair after camptothecin therapy.

Detailed Description
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RATIONALE: Many studies have tested the combination of cisplatin and irinotecan. Side effects have been well described. The two drugs are synergistic. The standard of care for colon cancer is the combination of 5-FU, leucovorin and irinotecan (Saltz regimen). Recently, oxaliplatin has been introduced for the treatment of colon cancer. Combination of oxaliplatin with 5FU (Folfox4) have shown comparable activity to the Saltz regimen. Furthermore, one author recently published on the triple combination of oxaliplatin, 5FU and irinotecan, with impressive clinical activity in colon cancer. There is some evidence that 5FU impairs DNA repair. One of the putative resistance mechanism to topoisomerase I inhibitors is increased DNA repair. We therefore hypothesize that inhibition of DNA repair by capecitabine may increase the activity of the combination of cisplatin and irinotecan. This study is open to all patients with solid tumor who have failed a line of chemotherapy

Official Title
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Phase I Study Of Capecitabine in Combination With Cisplatin and Irinotecan in Patients With Advanced Malignancies.

Conditions
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Solid Tumors, Cancer

Intervention / Treatment
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* Drug: Capecitabine in Combination with Cisplatin and Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients, 18 years of age or older, with incurable advanced cancer for whom there is no effective therapy are eligible. Patients must have a life expectancy of at least 12 weeks. Patients must have a Zubrod performance status of 0-2. Patients must sign an informed consent. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,500 or cells/mm3 and platelet count >100,000/mm3 and absence of a regular red blood cell transfusion requirement. Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal. Exclusion Criteria: Patients with symptomatic brain metastases are excluded from this study. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial. Patients whose cancer progressed while receiving 5-FU, cisplatin or irinotecan.

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Capecitabine in Combination with Cisplatin and Irinotecan|Cisplatin 50 mg/m2 on day 1 (course 1) or day 11 (subsequent courses) Irinotecan 50 mg/m2 on day 1, 8, and 15 (course 1) or day 11, 18 and 25 (subsequent courses). Capecitabine will be administered from day 1 to day 10 PO starting on course 2.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety/feasibility of Capecitabine with the combination of Cisplatin and Irinotecan. To determine the Phase II recommended dose and toxicity profile of Capecitabine with the combination of Cisplatin and Irinotecan. |  | Progressing disease or unacceptable toxicities | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study the biologic effect of pyrimidine inhibition on DNA repair after camptothecin therapy. |  | disease progression, unacceptable toxicities | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, solid tumors, DNA repair