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

NCT ID: NCT00019773

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-07-31

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.

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.

Conditions

Carcinoma of the Appendix; Colorectal Cancer; Small Intestine Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Surgery:

• Recovered from prior surgery

Other:

• At least 4 weeks since prior sorivudine or brivudine and recovered
• No concurrent sorivudine or brivudine
• No other concurrent investigational agents
• No other concurrent anticancer therapy or commercial agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Eva Szabo, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve. 2004 Mar;29(3):387-92. doi: 10.1002/mus.10559.

Reference Type: RESULT

PMID: 14981738 (View on PubMed)

Leonard G, Wright M, Quinn M, et al.: Survey of oxaliplatin-associated neurotoxicity with an interview-based questionnaire. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3018, 2003.

Reference Type: RESULT

Wilson RH, Lehky T, Thomas RR, Quinn MG, Floeter MK, Grem JL. Acute oxaliplatin-induced peripheral nerve hyperexcitability. J Clin Oncol. 2002 Apr 1;20(7):1767-74. doi: 10.1200/JCO.2002.07.056.

Reference Type: RESULT

PMID: 11919233 (View on PubMed)

Thomas R, Quinn M, Wilson R, et al.: A phase I trial of capecitabine (CAPE) & oxaliplatin (OHP). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-530, 2001.

Reference Type: RESULT

Other Identifiers

NCI-99-C-0117

Identifier Type: -

Identifier Source: secondary_id

MB-NAVY-99-01

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0011

Identifier Type: -

Identifier Source: secondary_id

CDR0000067201

Identifier Type: -

Identifier Source: org_study_id

NCT00001817

Identifier Type: -

Identifier Source: nct_alias