Oxaliplatin Plus Capecitabine in Treating Patients With Colorectal, Appendix, or Small Bowel Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00019773

Collaborator

(none)

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining oxaliplatin with capecitabine in treating patients who have colorectal, appendix, or small bowel cancer.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma of the Appendix Colorectal Cancer Small Intestine Cancer	Drug: capecitabine Drug: oxaliplatin	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of capecitabine when administered with oxaliplatin in patients with colorectal, appendiceal, or small bowel cancer.
Determine the clinical toxic effects associated with this regimen in these patients.
Characterize the molecular profile of tumor tissue obtained prior to study entry for determinants of sensitivity to this regimen in this patient population.
Characterize the molecular profile of a surrogate normal tissue (bone marrow aspirate) obtained prior to treatment and assess any potential drug-associated induction of DNA damage and inhibition of thymidylate synthase with a repeat bone marrow aspirate during therapy.
Assess any clinical activity of this regimen in this patient population.

OUTLINE: This is a dose-escalation study of capecitabine.

Patients receive oxaliplatin IV over 2 hours on day 1 followed by oral capecitabine twice daily on days 1-5 and 8-12. Courses repeat every 3 weeks in the absence of unacceptable toxicity or disease progression.

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.

Patients are followed every 3 months for 6 months.

PROJECTED ACCRUAL: A total of 106 patients will be accrued for this study within 36 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Pilot Study of Oxaliplatin in Combination With Capecitabine in Adult Cancer Patients

Study Start Date :

Jul 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed colorectal, appendiceal, or small bowel cancer
Measurable disease
No progression after prior capecitabine
No brain metastases or leptomeningeal carcinomatosis

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin normal
AST/ALT no greater than 2.5 times upper limit of normal

Renal:

Creatinine normal
Creatinine clearance greater than 60 mL/min

Cardiovascular:

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No sensory neuropathy
No history of allergy to platinum compounds
No history of allergy to antiemetics appropriate for administration during study
No history of intolerance to fluorouracil
No uncontrolled concurrent illness that would preclude study entry
No ongoing or active infection requiring IV antibiotics
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

See Disease Characteristics
Recovered from prior chemotherapy
No more than 2 prior systemic chemotherapy regimens for metastatic disease
At least 6 weeks since prior nitrosoureas or mitomycin
At least 8 weeks since prior eniluracil
At least 3 months since prior suramin
At least 4 weeks since other prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

Recovered from prior radiotherapy
At least 2 weeks since prior radiotherapy to no more than 20% of bone marrow reserve
At least 4 weeks since prior radiotherapy to at least 21% of bone marrow reserve