RAS and BRAF wild-type chemorefractory metastatic colorectal cancer patients MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: STIVARGA - 40 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - FLACONE (HDPE) - 3 FLACONI DA 28 COMPRESSE
Product Name: Regorafenib
Product Code: [Regorafenib]
Pharmaceutical Form: Film-coa
Sponsors
G.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age = 18 years. Histologically proven diagnosis of CRC. At least one measurable lesion according to RECIST1.1 ECOG PS = 1. mCRC previously treated for metastatic disease with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic monoclonal antibody (bevacizumab or aflibercept). RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of primary CRC or related metastasis (local laboratory assessment). Previous first-line anti-EGFR-containing therapy producing at least a partial response or a stable disease = 6 months. At least 4 months elapsed between the end of first-line anti-EGFR administration and screening. At least one line of therapy between the end of first-line anti-EGFR administration and screening. RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of ct-DNA at screening (central laboratory assessment by means of IdyllaTM ctKRAS-NRAS-BRAF Mutation Test, Biocartis, Inc.). Neutrophils = 1.5 x 109/L, Platelets =100 x 109/L, Hgb = 9 g/dl. Total bilirubin = 1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) = 2.5 x UNL (or =65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: Previous treatment with regorafenib. Radiotherapy to any site within 4 weeks before the study Untreated brain metastases or spinal cord compression or primary brain tumours. Evidence of bleeding diathesis or coagulopathy. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (= 6 months), myocardial infarction (= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment. Any previous venous thromboembolism = NCI CTCAE Grade 4. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to compare the efficacy in terms of OS of panitumumab followed after disease progression by regorafenib (arm A) versus the reverse sequence (arm B) in chemorefractory mCRC patients with previous benefit from first-line anti-EGFR-based treatment and with RAS/BRAF wt ct-DNA at the time of study entry.;Secondary Objective: Secondary objectives of this study are to evaluate the two proposed treatments in terms of: Duration of Progression-free Survival during the first-line of study treatment (1st-PFS); Duration of Progression-free Survival during the second-line of study treatment (2nd-PFS); Duration of Time to failure strategy (TFS); Objective Response Rate (ORR) during panitumumab and regorafenib; Overall Toxicity Rate; G3/4 Toxicity Rate; Translational analyses.;Primary end point(s): The primary endpoint is Overall Survival defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1st-Progression free survival (1st-PFS) is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumour assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumour assessments after baseline will have time to event censored on the date of randomization.; 2nd-Progression free survival (2nd-PFS) is defined as the time from the beginning of the second-line study treatment to the documentation of objective disease progression according to RECIST 1.1 criteria or death due to any cause, whichever occurs first. 2nd-PFS will be censored on the date of the last evaluable on study tumour assessment documenting absence of progressive disease for patients who are alive, on study and 2nd-progression free at the time of the analysis. 2nd-PFS will be analysed both in all patients who initiate a 2nd line (whichever 2nd-line treatment will be adopted) and in the per-protocol population;Timepoint(s) of evaluation of this end point: 6 months; 6 months | — |
Countries
Italy
Contacts
Public ContactUfficio Sperimentazioni sede operat
Fondazione GONO
Outcome results
None listed