Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Irinotecan, Oxaliplatin, and Capecitabine in Treating Patients With Unresectable Solid Tumors

Basic Trial Information

Objectives

1. Determine the maximum tolerated dose of irinotecan, oxaliplatin, and capecitabine in patients with unresectable solid tumors.
2. Determine the activity of this regimen in these patients.
3. Determine the toxicity profile, especially pertaining to hematologic and gastrointestinal toxicity, of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
  • Unresectable disease
• Willing to provide biologic specimens to determine UGT1A1 genotype
• No CNS metastases
  • Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy
• No concurrent immunotherapy
• No concurrent prophylactic colony-stimulating factor therapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of the bone marrow
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• No other concurrent investigational therapy
• No concurrent sorivudine, brivudine, lamivudine, or stavudine
• No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or 7/7 UGT1A1 genotype)
• AST no greater than 3 times ULN (5 times ULN if there is liver involvement)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy
• No uncontrolled infection
• No seizure disorder
• No peripheral neuropathy grade 2 or greater

Expected Enrollment

A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II [closed to accrual as of 8/24/06] , and 24-34 for stratum III) will be accrued for this study within approximately 4.4 years.

Outline

This is a dose-escalation study. Patients are stratified according to UGT1A1 genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).

Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 2-15. Courses repeat every 3 weeks.

Cohorts of 3-6 patients receive escalating doses of irinotecan, oxaliplatin, and 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. Once the MTD is determined, an additional 6-10 patients (for a total of 12 patients) receive treatment at that dose.

Patients are followed at 3 months.

Goetz MP, Safgren S, Goldberg RM, et al.: A phase I dose escalation study of irinotecan (CPT-11), oxaliplatin (Oxal), and capecitabine (Cap) within three UGT1A1 TA promoter cohorts (6/6, 6/7, and 7/7). [Abstract] J Clin Oncol 23 (Suppl 16): A-2014, 138s, 2005.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Matthew Goetz, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Matthew Ames, PhD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Registry Information
Official Title		A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
Trial Start Date		2003-11-06
Trial Completion Date		2010-07-09
Registered in ClinicalTrials.gov		NCT00074321
Date Submitted to PDQ		2003-11-06
Information Last Verified		2007-05-06
NCI Grant/Contract Number		CA15083, CA69912

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