Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal (BEYOND)
Colorectal Cancer Metastatic
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Clinical trial, phase II, Aged (at least 18 years old), Progression -Free - Survival, Safety, Conversion rate of RAS/BRAF status in liquid biopsy, Chemotherapy regimen, Monoclonal antibody, FOLFIRI, Panitumumab, RAS/BRAF Wild-type
Eligibility Criteria
Inclusion Criteria:
- Man or woman at least 18 years old
- Capable of understand, sign and date an informed consent approved by an IEC (investigational Ethics Committee)
- Histologically confirmed adenocarcinoma of the colon or rectum in subjects with metastatic disease
- Having received a 1st line chemotherapy regimen for mCRC consisting of FOLFOX + panitumumab and having at least achieved stable disease ( i.e., CR (Complete Response) PR (Partial Response) or SD (stable disease) )
- Wild-type RAS tumour status confirmed in liquid biopsies before starting second-line treatment
- At least one unidimensionally measurable lesion of at least 10 mm per RECIST criteria (version 1.1)
- Subjects not candidates for metastasectomy
- Tumour disease staging according to RECIST (version 1.1) by investigator up to 4 weeks prior to start of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL
Hepatic, renal and metabolic function as follows:
- Total bilirubin count ≤1.5 x upper limit of normal (ULN), ALT (alanine aminotransferase) and AST (aspartate aminotransferase) <2.5 x ULN; or in case of liver metastasis ALT and AST <5 x ULN
- Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥ 50 mL/min
- Magnesium > lower limit of normal (LLN) -
Exclusion Criteria:
- Diagnosis of progressive disease more than 3 months after the last panitumumab administration
- First-line PFS of less than 3 months
- Subjects given less than 3 months (consecutive) of first-line panitumumab
- History of prior or concurrent central nervous system (CNS) metastases
- History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 5 years before inclusion
- Prior irinotecan therapy
- Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the subject unfit for inclusion
- Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤ 30 days before inclusion (excluding panitumumab)
- Any investigational agent within 30 days prior to inclusion
- Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
- History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography
- Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03)
- Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
- History of Gilbert disease or known dihydropyrimidine deficiency syndrome
- Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
- Treatment for systemic infection within 14 days before the start of study treatment
- History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results
- Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
- Pregnant or breastfeeding woman
- Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g., diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men
- The subject is unwilling or unable to meet the requirements of the study
- Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule. These conditions should be discussed with the subject before inclusion in the trial. -
Sites / Locations
- ICO Girona Dr. Josep Trueta
- Hospital de Granollers
- Hospital Mutua de Terrassa
- Hospital General Universitario de Elche
- Hospital Universitario Fundación Alcorcón
- H. Universitari Sant Joan de Reus
- Hospital de La Ribera de Alzira
- Hospital Universitario Vall d'Hebron
- Hospital Clínic de Barcelona
- Hospital de la Santa Creu I Sant Pau
- Hospital 12 de Octubre
- Hospital Universtiario la Paz
- CIOCC Sanchinarro
- Complejo Hospitalario de Navarra
- Corporació Sanitaria Parc Taulí
- Fundación Instituto Valenciano de Oncología
- Hospital Universitario Dr. Peset
- Hospital Universitario y Politécnico La Fe
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
FOLFIRI + panitumumab
FOLFIRI
Patients received panitumumab plus FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses: Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy FOLFIRI: Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1 Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
Patients received FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses: Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1 Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2