Clinical trial NCT00019773: Oxaliplatin Plus Capecitabine in Treating Patients With Colorectal, Appendix, or Small Bowel Cancer
Official title: Pilot Study of Oxaliplatin in Combination With Capecitabine in Adult Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma of the Appendix
Colorectal Cancer
Small Intestine Cancer
Keywords: stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
stage 0 colon cancer
stage 0 rectal cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
small intestine adenocarcinoma
small intestine lymphoma
small intestine leiomyosarcoma
recurrent small intestine cancer
carcinoma of the appendix
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Eva Szabo, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.