A Phase I-II Study of Capecitabine and Oxaliplatin in Chemotherapy-Naive and Thymidylate Synthase Inhibitor Pretreated Advanced or Metastatic Colorectal Cancer
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
A Phase I-II Study of Capecitabine and Oxaliplatin in Chemotherapy-Naive and Thymidylate Synthase Inhibitor Pretreated Advanced or Metastatic Colorectal Cancer
OBJECTIVES: I. Determine the maximum tolerated dose of capecitabine when combined with
oxaliplatin in patients with chemotherapy naive or thymidylate synthase inhibitor pretreated
unresectable, advanced or metastatic colorectal cancer. II. Determine the safety profile,
toxicity, and efficacy of this regimen in these patients. III. Determine the complete and
partial remission rates, time to treatment failure, and overall survival of patients treated
with this regimen.
OUTLINE: This is a dose escalation, multicenter study of capecitabine. Patients are
stratified by pretreatment status (any pretreatment vs chemotherapy naive vs thymidylate
synthase inhibitor pretreatment). Phase I : Patients receive oxaliplatin IV over 2 hours on
day 1 and oral capecitabine every 12 hours on days 1-14. Treatment repeats every 3 weeks 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 highest dose at which 2 or more of 6 patients experience dose limiting
toxicity. Phase II: Patients receive capecitabine at the feasible dose. The feasible dose is
defined as the dose immediately preceding the MTD from phase I. Patients are followed every
3 months for 1 year, and then every 6 months thereafter until death.
PROJECTED ACCRUAL: Approximately 18 patients will be accrued for phase I of the study and a
total of 27-68 patients (14-25 thymidylate synthase inhibitor pretreated patients and 13-43
chemotherapy naive patients) will be accrued for phase II of the study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically proven unresectable, advanced or
metastatic colorectal cancer Measurable disease Phase I: Any pretreatment status Phase
II-N (chemotherapy naive patients): No prior chemotherapy for advanced or metastatic
cancer and no prior adjuvant chemotherapy OR No prior chemotherapy for advanced or
metastatic cancer and prior adjuvant chemotherapy ended more than 6 months ago Phase II-P
(thymidylate synthase inhibitor pretreated patients): No thymidylate synthase inhibitor
based regimen for advanced or metastatic cancer and prior adjuvant chemotherapy ended less
than 6 months ago OR One thymidylate synthase inhibitor based regimen for advanced or
metastatic cancer and no adjuvant thymidylate synthase inhibitor based regimen OR One
thymidylate synthase inhibitor based regimen for advanced or metastatic cancer and one
additional adjuvant thymidylate synthase inhibitor based regimen ended more than 6 months
ago No CNS metastases
PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: 0 or 1 Life expectancy: At
least 3 months Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3
Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no
greater than 2 times ULN (5 times ULN if related to liver metastases) Renal: Creatinine no
greater than 1.25 times ULN Cardiovascular: No New York Heart Association class III or IV
heart disease No congestive heart failure No symptomatic coronary artery disease No
cardiac arrhythmia unless well controlled with medication No myocardial infarction within
the past 12 months Neurologic: No peripheral neuropathy of any origin worse than grade 1
No prior or concurrent seizures or CNS disorder requiring treatment Other: Not pregnant
Negative pregnancy test Fertile patients must use effective contraception No dysphagia,
malabsorption, or intestinal obstruction that could impact the absorption or excretion of
study drug No psychiatric disability precluding informed consent or compliance No prior
malignancy within the past 5 years except adequately treated carcinoma in situ of the
cervix or localized nonmelanomatous skin cancer No other significant medical condition
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: At
least 4 weeks since prior major gastrointestinal surgery
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Markus M. Borner, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University Hospital Inselspital, Berne
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 41/99
NCT ID:
NCT00004187
Start Date:
June 1999
Completion Date:
April 2004
Related Keywords:
- Colorectal Cancer
- stage III colon cancer
- stage IV colon cancer
- stage III rectal cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
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