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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00074321
Recruitment Status : Completed
First Posted : December 11, 2003
Last Update Posted : June 6, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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. 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 or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: irinotecan hydrochloride Drug: oxaliplatin Drug: capecitabine Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:


I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).

II. To identify any activity of this treatment combination in patients with metastatic cancer.

III. To examine the differences in the toxicity profile, especially pertaining to hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.

IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its metabolites.

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 hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, 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.

After completion of study treatment, patients are followed up 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
Study Start Date : November 2003
Actual Primary Completion Date : July 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E

Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP

Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda

Other: laboratory biomarker analysis
Correlative studies

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0 [ Time Frame: 3 weeks ]

Secondary Outcome Measures :
  1. Incidence of UTG1A1*28 polymorphism [ Time Frame: Up to 3 months ]
    The overall incidence of UTG1A1*28 polymorphism will be estimated and summarized in this patient population. In addition, the incidence of this polymorphism will be explored in relation to tumor type.

  2. Adverse events profile assessed using NCI CTCAE v3.0 [ Time Frame: Up to 3 months ]
    The number and severity of all adverse events (overall, by dose level, and by tumor group) will be tabulated and summarized for the three patient groups. The grade 3+ adverse events will also be described and summarized in a similar fashion.

  3. Toxicity profile assessed using NCI CTCAE v3.0 [ Time Frame: Up to 3 months ]
    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized in each of the two groups. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  4. Response profile using RECIST criteria [ Time Frame: Up to 3 months ]
    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as table and progressive disease in the two patient populations (overall and by tumor group).

  5. Time until any treatment related toxicity [ Time Frame: Up to 3 months ]
    Will be summarized descriptively.

  6. Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ]
    Will be summarized descriptively.

  7. Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months ]
    Will be summarized descriptively.

  8. Time to progression [ Time Frame: Up to 3 months ]
    Will be summarized descriptively.

  9. Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ]
    Will be summarized descriptively.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • Performance status - ECOG 0-2
  • At least 12 weeks
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.0 g/dL
  • 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)
  • Creatinine no greater than 1.5 times ULN
  • No New York Heart Association class III or IV heart disease
  • 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
  • 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
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
  • No other concurrent chemotherapy
  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy to more than 25% of the bone marrow
  • No concurrent radiotherapy
  • See Disease Characteristics
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00074321

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Matthew Goetz Mayo Clinic

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00074321     History of Changes
Other Study ID Numbers: NCI-2012-01444
First Posted: December 11, 2003    Key Record Dates
Last Update Posted: June 6, 2013
Last Verified: June 2013

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors