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

NCT01639326 | Unknown Phase 2

• 1 other identifier: IIBSP-IRI-2011-134
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• Overall objective response rate (RR) by RECIST criteria v1.1

  The objective response rate, defined as the percentage of subjects who achieved a complete response (CR) or partial (PR) response will be evaluated according to RECIST criteria version 1.1

  24 months

Secondary Outcomes (4)

• Adverse Events

  24 months

• Progression free survival

  24 months

• Overall survival

  24 months

• overall response duration

  24 months

Study Arms (2)

Irinotecan high doses

EXPERIMENTAL

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.

Drug: Irinotecan high doses

Irinotecan standard doses

ACTIVE COMPARATOR

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

Drug: Irinotecan standard doses

Interventions

Irinotecan high doses 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 high doses

Irinotecan standard doses 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.

Irinotecan standard doses

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic colorectal adenocarcinoma not curable surgically.
• 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:
• \- Adequate renal function with creatinine levels \<1.5 mg / dL. BUN\> 50 ml / min

You may not qualify if:

• 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.
• Patients with significant neurological or psychiatric disorders, including dementia or poorly controlled epilepsy.
• Patients with any contraindications specified in the Summary of study drug.

Sponsors & Collaborators

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

Study Sites (3)

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

RECRUITING

Hospital de Mataró

Mataró, Catalunya/Barcelona, Spain

RECRUITING

Hospital Universitari Mutua de Terrassa

Terrassa, Catalunya/Barcelona, 08221, Spain

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• David Páez, MD

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

  PRINCIPAL INVESTIGATOR

• Montserrat Baiget, MD

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

  STUDY CHAIR

Central Study Contacts

Montserrat Baiget, MD

CONTACT

+34 93 553 56 37; MBaiget@santpau.cat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2012
• First Posted: July 12, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2018
• Study Completion: September 1, 2018
• Last Updated: May 7, 2015

Record last verified: 2012-06

Locations

ES (3)