Oxaliplatin, Irinotecan, and Capecitabine as a Combination Regimen for First-Line Treatment of Advanced or Metastatic Colorectal Cancer
18 Years
70 Years
Both
Colorectal Cancer
Trial Information
Oxaliplatin, Irinotecan, and Capecitabine as a Combination Regimen for First-Line Treatment of Advanced or Metastatic Colorectal Cancer
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of capecitabine
administered in combination with oxaliplatin and irinotecan in patients with
unresectable advanced or metastatic colorectal cancer. (Phase I)
- Determine the efficacy of this regimen in these patients. (Phase II)
Secondary
- Determine the tolerability of this regimen in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a
phase II study.
- Phase I: Patients receive oxaliplatin IV over 2 hours on days 1 and 15, irinotecan IV
over 1 hour on days 8 and 22, and oral capecitabine twice daily on days 1-29. Treatment
repeats every 5 weeks for up to 6 courses in the absence of disease progression or
unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive capecitabine at the MTD and irinotecan and oxaliplatin as in
phase I.
After completion of study treatment, patients are followed every 2 months for 1 year and
then every 4 months thereafter.
PROJECTED ACCRUAL: A total of 23-32 patients (3-12 for the phase I portion and 20 for the
phase II portion) will be accrued for this study within 2.75 years
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed unresectable advanced or metastatic
colorectal cancer
- Measurable disease (phase II only)
- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan or MRI
- No presence or history of CNS metastases
PATIENT CHARACTERISTICS:
Age
- 18 to 70
Performance status
- WHO 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin ≤ 1.25 times upper limit of normal (ULN) (1.5 times ULN if liver metastases
are present)
- AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
Renal
- Creatinine clearance > 60 mL/min
Cardiovascular
- No New York Heart Association class III-IV congestive heart failure
- No symptomatic coronary artery disease
- No uncontrolled cardiac arrhythmia
- No myocardial infarction within the past year
- No other clinically significant cardiac disease
Immunologic
- No active autoimmune disease
- No uncontrolled infection
- No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to
fluorouracil
- No known hypersensitivity to any component of study drugs
Other
- Not pregnant or nursing
- Negative pregnancy test
- Patients must use effective contraception during and for 1 year after study
participation
- No other malignancy within the past 5 years except adequately treated carcinoma in
situ of the cervix or localized nonmelanoma skin cancer
- No peripheral neuropathy > grade 1 of any origin (e.g., alcohol or diabetes)
- No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or
absorption of oral medication
- No psychiatric disability that would preclude study compliance
- No uncontrolled diabetes
- No other serious underlying medical condition that would preclude study participation
- No known dihydropyrimidine dehydrogenase deficiency
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent prophylactic hematopoietic growth factors
Chemotherapy
- More than 6 months since prior adjuvant fluoropyrimidine chemotherapy
- No other prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No concurrent radiotherapy
- Concurrent radiotherapy of a single painful lesion allowed
Surgery
- Not specified
Other
- More than 30 days since prior clinical trial participation
- No other concurrent experimental drugs
- No other concurrent anticancer therapy
- No concurrent sorivudine or its chemically-related analogues (e.g., lamivudine)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
capecitabine + oxaliplatin + irinotecan dose finding
Outcome Description:
Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I)
Outcome Time Frame:
30 days
Safety Issue:
Yes
Principal Investigator
Razvan Popescu, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Centre Hospitalier Universitaire Vaudois
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 41/03
NCT ID:
NCT00217711
Start Date:
May 2005
Completion Date:
October 2011
Related Keywords:
- Colorectal Cancer
- stage III colon cancer
- stage IV colon cancer
- stage III rectal cancer
- stage IV rectal cancer
- Colorectal Neoplasms
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