Clinical trial NCT00544063: Capecitabine, Irinotecan, and Oxaliplatin in Treating Patients With Metastatic Cancer
Official title: Phase I Study Evaluating the Feasibility of Chemotherapy With Capecitabine, Irinotecan, and Oxaliplatin in Patients With Metastatic Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-10-16
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose of capecitabine
measure: Dose-limiting toxicities
Secondary outcomes:
measure: Recommended phase II dose of capecitabine
measure: Toxicity profile
measure: Objective response
measure: Duration of response
measure: Time to disease progression
measure: Pharmacokinetic profile of capecitabine and irinotecan hydrochloride
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Marc Ychou, MD, PhD
References: