Phase I Study of Capecitabine in Combination With Cisplatin and Irinotecan

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

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

Study Overview

• Status: Completed
• Conditions: Cancer; Solid Tumors
• Intervention / Treatment: Drug: Capecitabine in Combination with Cisplatin and Irinotecan

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of New Mexico

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: November 2, 2005
• First Submitted That Met QC Criteria: November 3, 2005
• First Posted (Estimate): November 7, 2005

Study Record Updates

• Last Update Posted (Estimate): January 7, 2010
• Last Update Submitted That Met QC Criteria: January 6, 2010
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Phase I; solid tumors; DNA repair
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Irinotecan
• Other Study ID Numbers: 0103C