Irinotecan, Oxaliplatin, and Capecitabine in Treating Patients With Unresectable Solid Tumors - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00074321

Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan, oxaliplatin, and capecitabine in treating patients with unresectable solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: capecitabine Drug: irinotecan hydrochloride Drug: oxaliplatin	Phase I

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer

Drug Information available for: Oxaliplatin Irinotecan U 101440E Irinotecan hydrochloride Capecitabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	84
Study Start Date:	November 2003
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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

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.

PROJECTED ACCRUAL: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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/mm^3
Platelet count at least 100,000/mm^3
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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074321

Locations

United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Matthew P. Goetz, MD	Mayo Clinic
Investigator:	Matthew M. Ames, PhD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

ClinicalTrials.gov Identifier:	NCT00074321 History of Changes
Other Study ID Numbers:	CDR0000344367, MAYO-MC0311, NCI-6240
Study First Received:	December 10, 2003
Last Updated:	July 23, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms
Oxaliplatin
Irinotecan
Capecitabine
Camptothecin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic

Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012