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.
- 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
- 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
- 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.