Capecitabine, Irinotecan, and Oxaliplatin in Treating Patients With Metastatic Cancer

Phase I Study Evaluating the Feasibility of Chemotherapy With Capecitabine, Irinotecan, and Oxaliplatin in Patients With Metastatic Carcinoma

RATIONALE: Drugs used in chemotherapy, such as capecitabine, irinotecan, and oxaliplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with irinotecan and oxaliplatin in treating patients with metastatic cancer.

Study Overview

• Status: Unknown
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: oxaliplatin

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicities of capecitabine.

Secondary

• Determine the recommended phase II dose of capecitabine.
• Define the toxicity profile.
• Evaluate potential antitumor activity in terms of objective response, duration of response, and time to disease progression.
• Evaluate the pharmacokinetic profile of capecitabine and irinotecan hydrochloride.

OUTLINE: This is a dose-escalation study of capecitabine conducted in two parts.

• Part I: Patients receive irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine twice daily on days 1-7. Treatment repeats every 2 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Cohorts of up to 6 patients receive escalating doses (up to 5 dosages) of capecitabine. The maximum tolerated dose (MTD) is defined as the dose at which 50% of patients experience toxicity during the first 2 courses of therapy.

• Part II: Patients receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine on days 1-7. Treatment repeats every 2 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Cohorts of up to 6 patients receive escalating doses (up to 7 dosages) of capecitabine. The MTD is defined as in part I.

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Recruiting
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
    • Contact: Marc Ychou, MD, PhD; Phone Number: 33-4-6761-3066; Email: mychou@valdorel.fnclcc.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed metastatic carcinoma

  • Primary tumor may be present
  • No curative therapy available or the patient achieved no response to prior standard therapy
  • Nonresectable metastatic disease
• Measurable, evaluable, or nonevaluable disease

Exclusion criteria:

• Symptomatic brain metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Bilirubin < 1.25 times upper limit of normal (ULN) (1.5 times ULN if due to liver metastases)
• Transaminases < 3 times ULN (5 times ULN if due to liver metastases)
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Creatinine clearance > 30 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception

Exclusion criteria:

• Severe concurrent infection or major organ failure, including any of the following:

  • Cardiac disease
  • Diabetic decompensation
  • Clinically active infection
• Prior severe toxicity from fluorouracil
• Intestinal obstruction or subobstruction
• Malabsorption syndrome
• Peripheral neuropathy
• Uncontrolled epilepsy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• At least 4-6 weeks since prior anticancer chemotherapy

Exclusions criteria:

• Prior chemotherapy with any of the study drugs
• Prior major intestinal resection
• Concurrent participation in another clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose of capecitabine
Dose-limiting toxicities

Secondary Outcome Measures

Outcome Measure
Objective response
Time to disease progression
Duration of response
Toxicity profile
Recommended phase II dose of capecitabine
Pharmacokinetic profile of capecitabine and irinotecan hydrochloride

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Marc Ychou, MD, PhD, Institut du Cancer de Montpellier - Val d'Aurelle

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: October 13, 2007
• First Submitted That Met QC Criteria: October 13, 2007
• First Posted (Estimate): October 16, 2007

Study Record Updates

• Last Update Posted (Estimate): December 15, 2009
• Last Update Submitted That Met QC Criteria: December 13, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Oxaliplatin; Irinotecan
• Other Study ID Numbers: CDR0000564073; CLCC-XEL-IRIN-OX; INCA-RECF0416; VA-XIOX; EudraCT-2005-004567-38