REGORAFENIB for Metastatic colorectal cancer (RAS-mutant)

Inclusion criteria

• {"criterion_text":"- Written informed consent to study procedures and to correlative studies.\n- Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL.\n- Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN\n- Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula)\n- Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range.\n- Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory\n- Either sex aged ≥ 18\n- Histologically proven of colorectal adenocarcinoma\n- Diagnosis of metastatic disease.\n- RAS mutant at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status\n- Achieved a PFS in first line > 6 months with chemotherapy in combination to antiangiogenic treatment OR with one metastatic site at study entry\n- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry\n- Imaging-documented measurable disease, according to RECIST 1.1 criteria.\n- Estimated life expectancy of more than 12 weeks"}

Exclusion criteria

• {"criterion_text":"- 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.\n- Any contraindication to regorafenib.\n- Not received immunotherapy if dMMR or MSI-H\n- Major surgical intervention within 4 weeks prior to enrollment.\n- Pregnancy and breast-feeding.\n- Any brain metastasis.\n- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study.\n- History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form.\n- Participation in any interventional drug or medical device study within 30 days prior to treatment start.\n- Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment\n- Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD)."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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."}

Secondary endpoints

• {"endpoint_text":"- 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. PFS will be censored at the time of the last available tumor assessment documenting absence of progressive disease for patients alive at the time of analysis.","definition_or_measurement_approach":"Time from randomization until first documented disease progression or death from any cause; censoring at last tumor assessment documenting absence of progression for patients alive at analysis."}
• {"endpoint_text":"- Overall survival (OS) calculated as the time from randomization until the date of death from any cause. OS will be censored at the last date the patient was known to be alive for patients alive at the time of analysis","definition_or_measurement_approach":"Time from randomization until death from any cause; censored at last known alive date."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients with complete or partial response per RECIST 1.1 relative to total enrolled."}
• {"endpoint_text":"- Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response.","definition_or_measurement_approach":"Proportion of patients whose best response is complete response, partial response, or stable disease."}
• {"endpoint_text":"- Progression free survival 2 (PFS2) calculated as the time from registration to progression from subsequent line of treatment or death without progression, whichever occurred first.","definition_or_measurement_approach":"Time from registration to progression on next line of treatment or death without progression, whichever occurs first."}
• {"endpoint_text":"- Overall Toxicity rate defined as adverse events graded according NCI CTCAE v 5.0. as the proportion of patients experiencing any grade AE accordingly to the NCI Common Terminology Criteria of Adverse Events (NCI CTC-AE) Version 5, relative to the total of patients receiving at least one cycle of treatment.AE will be listed individually by the patient and summarized overall (severity grades 1-4) and for grade ≥3 by treatment received.","definition_or_measurement_approach":"Proportion of patients experiencing any grade adverse event per NCI CTCAE v5.0 among those receiving at least one cycle; AEs listed individually and summarized by grade."}
• {"endpoint_text":"- Quality of life (QoL) investigated through the EORTC QOL-C30 and CR29 questionnaires at baseline (prior to treatment start, once eligibility is confirmed) and every 8 weeks from randomization until disease progression, treatment failure or death.","definition_or_measurement_approach":"EORTC QLQ-C30 and CR29 questionnaires administered at baseline and every 8 weeks from randomization until progression, treatment failure or death."}
• {"endpoint_text":"- PRO-CTCAE questionnaires will be administered at the same time points with items dedicated in particular to Hand-Foot Syndrome and Hand-Foot skin reactions, diarrhea and neuropathy, to better evaluate the effect of two different strategies of treatment on the health-related QoL.","definition_or_measurement_approach":"PRO-CTCAE administered at same schedule with items focused on HFS, diarrhea, and neuropathy to evaluate treatment strategy effects on HRQoL."}
• {"endpoint_text":"- Time/toxicity defined as time spent coordinating treatments and in-visits to a health care facility (including travel and waiting), seeking urgent/emergent care for side effects, hospitalizations, and follow-up tests and rehabilitation (measured as Days with Physical Health Care System Contact","definition_or_measurement_approach":"Measured as days with physical health care system contact including travel, waiting, urgent care, hospitalizations and follow-up tests/rehabilitation."}
• {"endpoint_text":"- Financial toxicity assessed through the PROFFIT questionnaire at baseline (prior to treatment start, once eligibility is confirmed) and every 8 weeks from randomization until disease progression, treatment failure or death.","definition_or_measurement_approach":"PROFFIT questionnaire administered at baseline and every 8 weeks from randomization until progression, treatment failure or death to assess financial toxicity."}

Italy

Earliest CTIS Part Ii Submission Date

28-04-2025

Latest Decision Or Authorization Date

02-10-2025

Processing Time Days

157

Number Of Sites

9

Number Of Participants

60

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy