Rechallenge of Cetuximab Combined With Irinotecan as Third-line Chemotherapy in Patients With Metastatic Colorectal Cancer - Phase II Study (REGAIN)

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Cancer, Colorectal, Metastatic, Thrid-line, Irinotecan, Cetuximab Read More

Inclusion Criteria:

• Signed and dated informed consent
• Histologically confirmed metastatic adenocarcinoma of the colon or rectum
• All Wild Type KRAS (exon 2 [codons 12-13], exon 3 [codons - 61]; exon 4 [codon 146]), NRAS (exon 2 [ codons 12-13] and exon 3 [codon 61) and BRAF (V600E) tumor ( local assessment performed either on primary tumor or metastasis)
• First line chemotherapy regimen with a fluoropyrimidine and Irinotecan (FOLFIRI) + cetuximab with initial partial or complete response and progressive disease (PD) with PD ≤ 6 weeks after the last administration of cetuximab
• Other line(s) of therapy(ies) including the following drugs: second line oxaliplatin based chemotherapy with fluoropyrimidines (5FU or capecitabine) + bevacizumab and eventually regorafenib (possible but not mandatory) and progression or limiting toxicity to the last therapy with a minimum of 4 months between last injection of cetuximab and inclusion in this study
• At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 (All sites must be evaluated ≤ 28 days prior to the enrolment)
• Age ≥18 years
• World Health Organization (WHO) Performance status (PS) 0-2
• The patient has adequate organ function, defined as :

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 100 x 109/L.Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times ULN, Serum creatinine level <150μM/l

• For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug
• Men and women are required to use adequate birth control during the study (when applicable) and until 6 months after the end of study treatment
• Registration in a national health care system (CMU included)

Exclusion Criteria:

• Previous chemotherapy other than adjuvant therapy with different combinations than those scheduled in first and second line treatment
• Presence of any KRAS, BRAF or NRAS mutation by allelic discrimination on tumor DNA
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not)
• History or evidence of central nervous system metastasis (systematic CT-scan or MRI not mandatory if no clinical symptoms)
• Known allergy or hypersensitivity to cetuximab
• Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study
• Active or uncontrolled clinically serious infection
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
• Other serious and uncontrolled non-malignant disease
• Pregnancy
• Breast feeding
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Known Gilbert's syndrome
• Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine
• Concomitant use with St John's Wort
• Chronic inflammatory bowel disease and/or Bowel obstruction