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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00074321
First received: December 10, 2003
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: irinotecan hydrochloride
Drug: oxaliplatin
Drug: capecitabine
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of UTG1A1*28 polymorphism [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    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.

  • Adverse events profile assessed using NCI CTCAE v3.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Toxicity profile assessed using NCI CTCAE v3.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Response profile using RECIST criteria [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    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).

  • Time until any treatment related toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Will be summarized descriptively.

  • Time to progression [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Will be summarized descriptively.

  • 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 ] [ Designated as safety issue: No ]
    Will be summarized descriptively.


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

Detailed Description:

OBJECTIVES:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Matthew Goetz Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00074321     History of Changes
Other Study ID Numbers: NCI-2012-01444, MC0311, NCI-6240, CDR0000344367, MAYO-MC0311
Study First Received: December 10, 2003
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Irinotecan
Camptothecin
Capecitabine
Oxaliplatin
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014