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

Institut du Cancer de Montpellier - Val d'Aurelle

Status and phase: Unknown; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: oxaliplatin; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT00544063

INCA-RECF0416

CDR0000564073

EudraCT-2005-004567-38

CLCC-XEL-IRIN-OX

VA-XIOX

Details and patient eligibility

About

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.

Full 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.

Enrollment: 33 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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