Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer
|ClinicalTrials.gov Identifier: NCT02573220|
Recruitment Status : Withdrawn (Study terminated by PI due to inability to accrue.)
First Posted : October 9, 2015
Last Update Posted : December 9, 2016
|Condition or disease||Intervention/treatment||Phase|
|Stage IVA Colorectal Cancer Stage IVB Colorectal Cancer||Biological: Cetuximab Drug: Fluorouracil Drug: Irinotecan Hydrochloride Drug: Leucovorin Calcium||Phase 1|
I. To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the phase II recommended dosage of irinotecan (irinotecan hydrochloride) administered in the FOLFIRI regimen plus cetuximab in metastatic colorectal cancer (mCRC) patients with *1/*1 and *1/*28 uridine diphosphate glucuronosyltransferase (UGT1A1) genotype treated as first line chemotherapy.
To estimate the response rate, progression-free survival (PFS) and metastasectomy (with curative intent) rate in the overall patient population (both genotype cohorts).
I. To evaluate the variability of irinotecan pharmacokinetics, in combination with cetuximab, in patients with *1/*1 and *1/*28 genotype and the effect of the pharmacokinetic profile on toxicity and response rate.
II. To evaluate the pharmacokinetic profile of irinotecan and its major metabolites in the absence and the presence of cetuximab administration, in order to define the effect of the chimeric monoclonal antibody on irinotecan pharmacokinetics.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride in patients with UGT1A1.
Patients receive irinotecan hydrochloride intravenously (IV) over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A UGT1A1 Genotype-Guided Dosing Study of Irinotecan Administered in Combination With 5-Fluorouracil/Leucovorin (FOLFIRI) and Cetuximab as First-Line Therapy in RAS Wild-Type Metastatic Colorectal Cancer Patients|
|Study Start Date :||June 2015|
|Actual Primary Completion Date :||August 2016|
|Actual Study Completion Date :||August 2016|
Experimental: Treatment (FOLFIRI and cetuximab)
Patients receive irinotecan hydrochloride IV over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Irinotecan Hydrochloride
Drug: Leucovorin Calcium
- Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]The MTD recommended for phase II studies will be defined as the dose level immediately below the one at which 1 out of 3 patients or 1 out of 6 patients experienced DLT. Therefore at the MTD, 1/3 out of at least 10 patients experienced DLT. No intra-patient dose escalation is allowed. There will be two genotype cohorts of patients: one for each genotype. The cumulative hematological and non-hematological toxicities as well as the number of dose reductions and a delay in starting the next cycle of treatment will be used as secondary indicators to differentiate the two genotype cohorts of patients. Patients can continue receiving the same dose of irinotecan in the absence of major toxicity if before retreatment they fully recover from any non-hematological toxicity, absolute neutrophil count is 1500 microliters and platelet count is 100,000 microliters. Chemotherapy is discontinued on evidence of disease progression by RECIST version 1.1.
- Response rate [ Time Frame: Every 2 cycles (every 8 weeks), from the beginning of the study until disease progression or death, which ever comes first (up to on average 60 months) ]Response rate is the number of patients with a partial response (by RECIST version 1.1) divided by the total number of patients.
- Progression-free survival (PFS) [ Time Frame: From beginning of the study until disease progression or death, which every comes first (up to on average 60 months) ]PFS is the time (in days) between study enrollment and disease progression (by RECIST version 1.1) or death, whichever comes first.
- metastectomy (with curative intent) rate [ Time Frame: Within 1 year of starting therapy ]Metastatectomy rate is the number of patients who undergo a surgical resection with curative intent divided by the total number of patients
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573220
|Centro di Riferimento Oncologico|
|Aviano, Italy, 33081|
|Principal Investigator:||Manish Sharma||University of Chicago Comprehensive Cancer Center|