Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal (BEYOND)

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 Read More

Inclusion Criteria:

1. Man or woman at least 18 years old
2. Capable of understand, sign and date an informed consent approved by an IEC (investigational Ethics Committee)
3. Histologically confirmed adenocarcinoma of the colon or rectum in subjects with metastatic disease
4. 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) )
5. Wild-type RAS tumour status confirmed in liquid biopsies before starting second-line treatment
6. At least one unidimensionally measurable lesion of at least 10 mm per RECIST criteria (version 1.1)
7. Subjects not candidates for metastasectomy
8. Tumour disease staging according to RECIST (version 1.1) by investigator up to 4 weeks prior to start of study treatment
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
10. Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL

11. 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:

1. Diagnosis of progressive disease more than 3 months after the last panitumumab administration
2. First-line PFS of less than 3 months
3. Subjects given less than 3 months (consecutive) of first-line panitumumab
4. History of prior or concurrent central nervous system (CNS) metastases
5. 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
6. Prior irinotecan therapy
7. Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the subject unfit for inclusion
8. Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤ 30 days before inclusion (excluding panitumumab)
9. Any investigational agent within 30 days prior to inclusion
10. Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
11. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography
12. 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)
13. Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
14. History of Gilbert disease or known dihydropyrimidine deficiency syndrome
15. Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
16. Treatment for systemic infection within 14 days before the start of study treatment
17. History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results
18. Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
19. Pregnant or breastfeeding woman
20. 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
21. The subject is unwilling or unable to meet the requirements of the study
22. 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. -