The investigators hypothesize that patients with mCRC RAS-mutant eligible for a second line treatment with good prognostic features, identified as single metastatic site, long progression free survival (PFS) in first line treatment, might benefit from a personalized approach, with less intensive treatment with regorafenib as part of a continuum-of-care strategy aimed at ensuring quality of life and extending survival.
Written informed consent to study procedures and to correlative studies.
Either sex aged ≥ 18.
Histologically proven of colorectal adenocarcinoma.
Diagnosis of metastatic disease.
Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Any contraindication to regorafenib.
Not received immunotherapy if dMMR or MSI-H.
Major surgical intervention within 4 weeks prior to enrollment.
Parallel
standard second line treatment, at discretion of the investigator
DrugCombination treatment may include: 5FU/LFA, capecitabine, oxaliplatin, irinotecan, bevacizumab, aflibercept
Regorafenib (BAY73-4506)
DrugRegorafenib will be administered following a dose-escalation strategy: starting dose 80 mg/day orally with weekly escalation, per 40 mg increment up to 160 mg/day regorafenib); if no significant drug-related adverse events occurred for 21 days of a 28-day cycle. The following cycle will be administered at highest tolerated dose from cycle 1 (up to 160 mg), as per current guidelines and clinical practice. Treatment will continue until disease progression, unacceptable toxic effects, motivated decision to stop the treatment by the treating physician, or refusal or withdrawal of consent by the patient. Every cycle will be administered every 28 days (four weeks) +/- 3 days.
Progression Free Survival rate at 6 months in the two arms.
Progression Free Survival rate at 6 months(PFS rate at 6-months) is defined as the rate of assessable patients alive and not progressed after 6 months from study initiation (i.e randomization) to the first documentation of objective disease progression by RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Progression free survival (PFS)
Progression free survival (PFS) calculated as the time from randomization until the date of death from any cause until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
Overall survival (OS)
Overall survival (OS) calculated as the time from randomization until the date of death from any cause.
Objective Tumor Response Rate (ORR)
Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1, as the proportion of patients achieving complete or partial response relative to total enrolled patients.
Disease Control Rate (DCR)
Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response
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National Cancer Institute, Naples
Lead sponsor
BAYER S.p.A. - Italia
Collaborator
