Clinical trial NCT01639326: Study to Evaluate the Efficacy and Safety of FOLFIRI-AD in Patients With Metastatic Colorectal Cancer UGT1A Genotype 1
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2012-07-12
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Overall objective response rate (RR) by RECIST criteria v1.1
timeFrame: 24 months
Secondary outcomes:
measure: Adverse Events
timeFrame: 24 months
measure: Progression free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: overall response duration
timeFrame: 24 months
Other outcomes:
Locations:
city: Mataró
country: Spain
facility: Hospital de Mataró
state: Catalunya/Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua de Terrassa
state: Catalunya/Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: David Páez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Montserrat Baiget, MD
role: STUDY_CHAIR
References: