Irinotecan, Oxaliplatin, and Capecitabine in Treating Patients With Unresectable Solid Tumors
|ClinicalTrials.gov Identifier: NCT00074321|
Recruitment Status : Completed
First Posted : December 11, 2003
Last Update Posted : June 6, 2013
|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|
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)|
|Official Title:||A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors|
|Study Start Date :||November 2003|
|Primary Completion Date :||July 2010|
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
Other Names:Drug: oxaliplatin
Other Names:Drug: capecitabine
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
- 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 ]
- 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.
- 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.
- 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.
- 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).
- Time until any treatment related toxicity [ Time Frame: Up to 3 months ]Will be summarized descriptively.
- Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ]Will be summarized descriptively.
- Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months ]Will be summarized descriptively.
- Time to progression [ Time Frame: Up to 3 months ]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 ]Will be summarized descriptively.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00074321
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Matthew Goetz||Mayo Clinic|