Trial record 2 of 10 for:    ugt1a1 | Open Studies | Interventional Studies | colorectal cancer | irinotecan

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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier:
NCT01639326
First received: July 10, 2012
Last updated: January 22, 2013
Last verified: June 2012
  Purpose

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).


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Irinotecan high doses
Drug: Irinotecan standard doses
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Pharmacogenetic Study to Evaluate the Efficacy and Safety of FOLFIRI Schedule With High Doses of Irinotecan (FOLFIRI-AD) in Patients With Metastatic Colorectal Cancer According to UGT1A Genotype 1.

Resource links provided by NLM:


Further study details as provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:

Primary Outcome Measures:
  • Overall objective response rate (RR) by RECIST criteria v1.1 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The intensity of the adverse reactions are classified according to the system Toxicity Criteria NCI v 4.0.

  • Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Elapsed time from inclusion to the date of documented disease progression or death from any cause (whichever occurs first).

  • Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Elapsed time from inclusion to the time when death occurs from any cause. The subjects lost to follow up will be censored at the date of last follow up.

  • overall response duration [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    be measured from the date of the first documentation of RP or RC (whatever the state to register first) until the first date to register progression (PG) or death from any cause. Only in this analysis included subjects who achieved a CR or PR.


Estimated Enrollment: 96
Study Start Date: July 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Active Comparator: 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
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01639326

Contacts
Contact: Montserrat Baiget, MD +34 93 553 56 37 MBaiget@santpau.cat

Locations
Spain
Hospital de Mataró Recruiting
Mataró, Catalunya/Barcelona, Spain
Contact: Pilar Lines, MD         
Principal Investigator: Pilar Lines, MD         
Hospital Universitari Mutua de Terrassa Recruiting
Terrassa, Catalunya/Barcelona, Spain, 08221
Contact: Julen Fernandez, MD         
Principal Investigator: J. Fernandez, MD         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: David Páez, MD       DPaez@santpau.cat   
Principal Investigator: David Paez, MD         
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Investigators
Principal Investigator: David Páez, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Study Chair: Montserrat Baiget, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  More Information

No publications provided

Responsible Party: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier: NCT01639326     History of Changes
Other Study ID Numbers: IIBSP-IRI-2011-134
Study First Received: July 10, 2012
Last Updated: January 22, 2013
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Irinotecan
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014