Study to Evaluate the Efficacy and Safety of FOLFIRI-AD in Patients With Metastatic Colorectal Cancer UGT1A Genotype 1

NCT ID: NCT01639326

Last Updated: 2015-05-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2018-09-30

Brief Summary

This study aims to use the corresponding pharmacogenetic analysis to increase the dose of irinotecan in the schemes commonly used standard chemotherapy in advanced colorectal cancer treatment first. The project aims to improve the therapeutic index of chemotherapy. This optimization is raised based on the administration of different doses of the drug depending on the genotype UGT1A1 gene. The research team proposes this project to demonstrate how the administration of high doses of irinotecan in the FOLFIRI scheme in patients with genotype UGT1A1 favorable (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28), significantly improves the efficiency of the antineoplastic agent without significant increase in toxicity. Secondarily will assess the possible prognostic factors related to tolerance and efficacy.

The primary objective is to evaluate the efficacy of high doses of irinotecan in the FOLFIRI scheme in patients with metastatic colorectal cancer with a favorable genotype UGT1A1 (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan high doses

Patients will receive irinotecan dose of 300 mg / m² in patients UGT1A1 \* 1 / \* 1 and 260 mg / m² in patients UGT1A1 \* 1 / \* 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.

Group Type: EXPERIMENTAL

Irinotecan high doses

Intervention Type: DRUG

Irinotecan dose of 300 mg / m² in patients UGT1A1 \* 1 / \* 1 and 260 mg / m² in patients UGT1A1 \* 1 / \* 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.

Irinotecan standard doses

Patients will receive irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours

Group Type: ACTIVE_COMPARATOR

Irinotecan standard doses

Intervention Type: DRUG

Irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.

Interventions

Irinotecan high doses

Irinotecan dose of 300 mg / m² in patients UGT1A1 \* 1 / \* 1 and 260 mg / m² in patients UGT1A1 \* 1 / \* 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.

Intervention Type: DRUG

Irinotecan standard doses

Irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed metastatic colorectal adenocarcinoma not curable surgically.
• Not received prior systemic therapy for metastatic colorectal cancer. It allows receiving neoadjuvant or adjuvant chemotherapy (without irinotecan) as a treatment of the primary tumor at least six months before inclusion. All toxicities secondary to previous treatment should have been resolved before inclusion. The progression of disease (metastatic disease) should be confirmed radiologically after adjuvant treatment.
• Genotype of the gene UGT1A1 * 1 / * 1 or * 1 / * 28
• Age> or = 18 and <75 years.
• ECOG 0-1.
• Measurable disease according to RECIST version 1.1
• Life expectancy> or equal to 3 months.
• Informed consent, dated and signed.
• Adequate bone marrow function as:

Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl may be transfused before inclusion in the study) Platelet count ≥ 100 x 109 / L Absolute neutrophil count (ANC) ≥ 1.5x 109 / L - Adequate liver function as: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN in the absence of liver metastases and ALT and AST ≤ 5 × ULN in the presence of liver metastases Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN in the presence of liver metastases or ≤ 10 x ULN in the presence of bone metastases

• Adequate renal function with creatinine levels <1.5 mg / dL. BUN> 50 ml / min

Exclusion Criteria

• Genotype of the gene UGT1A1 * 28 / * 28 (Gilbert's syndrome)
• Patients who are pregnant or breast-feeding
• Concomitant treatment with other antineoplastic therapy other than specified.
• Patients with active infectious processes and patients with immunosuppressive therapy, or chronic anticoagulant therapy.
• History of malignancy in the last five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix treated properly.
• Patients with positive serology for HIV previously known, chronic diarrhea, inflammatory bowel disease or malabsorption syndrome or tumor obstruction unresolved.
• Clinically significant cardiovascular disease: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure grade II or higher NYHA or serious cardiac arrhythmia.
• Patients with significant neurological or psychiatric disorders, including dementia or poorly controlled epilepsy.
• Patients with any contraindications specified in the Summary of study drug.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Páez, MD

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Montserrat Baiget, MD

Role: STUDY_CHAIR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Site Status: RECRUITING

Hospital de Mataró

Mataró, Catalunya/Barcelona, Spain

Site Status: RECRUITING

Hospital Universitari Mutua de Terrassa

Terrassa, Catalunya/Barcelona, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Montserrat Baiget, MD

Role: CONTACT

MBaiget@santpau.cat

+34 93 553 56 37

Facility Contacts

David Páez, MD

Role: primary

DPaez@santpau.cat

Pilar Lines, MD

Role: primary

Julen Fernandez, MD

Role: primary

Other Identifiers

IIBSP-IRI-2011-134

Identifier Type: -

Identifier Source: org_study_id