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

Primary Purpose

Metastatic Colorectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Irinotecan high doses

Irinotecan standard doses

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hospital de MataróRecruiting
Hospital Universitari Mutua de TerrassaRecruiting
Hospital de la Santa Creu i Sant PauRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Irinotecan high doses

Irinotecan standard doses

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Adverse Events

The intensity of the adverse reactions are classified according to the system Toxicity Criteria NCI v 4.0.

Progression free survival

Elapsed time from inclusion to the date of documented disease progression or death from any cause (whichever occurs first).

Overall survival

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

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.

Full Information

NCT ID

NCT01639326

First Posted

July 10, 2012

Last Updated

May 6, 2015

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT01639326

Brief Title

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

Acronym

FOLFIRI-AD

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2012

Overall Recruitment Status

Unknown status

Study Start Date

July 2012 (undefined)

Primary Completion Date

July 2018 (Anticipated)

Study Completion Date

September 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Irinotecan high doses

Arm Type

Experimental

Arm Description

Arm Title

Irinotecan standard doses

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Irinotecan high doses

Intervention Description

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

Intervention Name(s)

Irinotecan standard doses

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Adverse Events

Description

The intensity of the adverse reactions are classified according to the system Toxicity Criteria NCI v 4.0.

Time Frame

24 months

Title

Progression free survival

Description

Elapsed time from inclusion to the date of documented disease progression or death from any cause (whichever occurs first).

Time Frame

24 months

Title

Overall survival

Description

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.

Time Frame

24 months

Title

overall response duration

Description

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Montserrat Baiget, MD

Phone

+34 93 553 56 37

MBaiget@santpau.cat

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Páez, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Montserrat Baiget, MD

Organizational Affiliation

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

Official's Role

Study Chair

Facility Information:

Facility Name

Hospital de Mataró

City

Mataró

State/Province

Catalunya/Barcelona

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pilar Lines, MD

First Name & Middle Initial & Last Name & Degree

Pilar Lines, MD

Facility Name

Hospital Universitari Mutua de Terrassa

City

Terrassa

State/Province

Catalunya/Barcelona

ZIP/Postal Code

08221

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Julen Fernandez, MD

First Name & Middle Initial & Last Name & Degree

J. Fernandez, MD

Facility Name

Hospital de la Santa Creu i Sant Pau

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Páez, MD

DPaez@santpau.cat

First Name & Middle Initial & Last Name & Degree

David Paez, MD

12. IPD Sharing Statement

Learn more about this trial

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

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