Metastatic colorectal cancer
Conditions
Interventions
Trade Name: STIVARGA
Product Name: Régorafenib
Pharmaceutical Form: Coated tablet
CAS Number: 755037-03-7
Other descriptive name: REGORAFENIB
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
CHU de Besançon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically proven metastatic colorectal cancer in progression after previous standard treatments (5FU, CPT11, oxaliplatin, anti-VEGF and anti-EGFR therapy if KRAS and NRAS WT), or not considered as candidate for these treatments 2. Life expectancy of at least 3 months 3. Female or male with age >18 years old 4. Performance status = 0 or 1 (Annex 1) 5. Measurable disease defined according to RECIST v1.1 guidelines (scanner or MRI) (Annex 2) 6. Adequate bone marrow, liver and renal functions. a. Haemoglobin = 9 g/dL; absolute neutrophil count (ANC) = 1.5 x 109/L; platelets = 100 x 109/L b. Total serum bilirubin = 1.5 times upper normal value (ULN), serum alkaline phosphatase 50 ml/min d. Proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
Exclusion criteria: Non-eligible to a clinical trial: 1. Diagnosis of additional malignancy within 2 years prior to the inclusion (exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical cancer), 2. Current participation in a study of an investigational agent or in the period of exclusion 3. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion in the trial ; 4. Patient under judicial protection (curatorship, tutorship) and/or deprived of freedom, Cancer-specific or treatment-specific exclusion criteria: 5. Planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment, 6. Previous exposition to regorafenib 7. Previous exposition to other anti-angiogenic treatment than bevacizumab and aflibercept 8. Complete deficit in dihydropyrimidine deshydrogenase (DPD), 9. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication, 10. Pregnant or breast-feeding subjects, 11. Congestive Heart Failure = New York Heart Association (NYHA) class 2, unstable angina (anginal symptomatology at rest), 12. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), 13. Myocardal infarction less than 6 months before start of study drug, 14. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted), 15. Uncontrolled hypertension (Systolic blood pressure >150 mmHg and/or diastolic pressure >100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy 16. Pleural effusion or ascites that causes respiratory compromise (= CTCAE grade 2 dyspnea), 17. Ongoing infection >grade 2 CTCAE V5, 18. Known History of human immunodeficiency virus (HIV) infection, 19. Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy, 20. Subjects with seizure disorder requiring medication, 21. History of organ allograft, 22. Subjects with evidence or history of any bleeding diathesis, irrespective of severity, 23. Any haemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication, 24. Serious, Non-healing wound, active ulcer or untreated bone fracture, 25. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion, 26. Dehydration CTCAE v4 grade =1, 27. Known hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation, 28. Interstitial lung disease with ongoing signs or symptoms, 29. Persistent proteinuria of CTCAE Grade 3 (>3.5 g/24 hours), 30. Subject unable to swallow oral medications, 31. Any malabsorption condition, unresolved toxicity higher than CTCAE (V4) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy = Grade 2, 32. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks, 33. Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN, 34. Chronic treatment with drug potentially interacti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this clinical trial is to assess the potential clinical interest of regorafenib in combination of metronomic chemotherapies and low-dose aspirin in patients with metastatic colorectal cancer carcinoma, previously exposed or not considered as candidate for 5FU, CPT11, oxaliplatin, anti-VEGF and anti-EGFR, by evaluation of the objective response rate (ORR) during treatment period;Secondary Objective: 1. To investigate the impact of regorafenib and metronomic chemotherapy on overall survival (OS) 2. To investigate the impact of regorafenib and metronomic chemotherapy on progression-free survival (PFS) 3. To investigate the impact of combined treatment on patient’s health related quality of life (QoL) 4. To evaluate the safety of regorafenib in association with metronomic chemotherapies 5. To correlate CHUN morphologic criteria with RECIST v1.1 response ;Primary end point(s): The objective response rate (ORR) will be defined by RECIST v1.1 criteria (Annex 2) as the best disease response observed during the treatment period. ORR rate is defined as the proportion of patients whose tumor regresses or does not progress under treatment.;Timepoint(s) of evaluation of this end point: during the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival (OS): defined as the time from the treatment start date to death from any cause 2. Progression-free survival (PFS): defined as the time from the treatment start date to disease progression or death from any cause 3. Health related Quality of life : o EORTC QLC30 + CR29, EQ-5D-3L questionnaires (Annex 3, 4, 5) o TUDD (Time Until Definitive Deterioration) of 5 targeted dimensions : Global health/ Pain/ Physical Functioning/ Fatigue / Emotional Functioning o Number and volumes of paracentesis and drainages (ascite or pleural effusions) o Number of days of hospitalization o Number of days taking level 3 analgesics 4. Toxicities graded according to NCI-CTCAE criteria version 5 (Annex 6) 5. Evaluation of CHUN morphological criteria and correlation with response according to RECIST v1.1 and serum stromal biomarkers (Annex 7). ;Timepoint(s) of evaluation of this end point: date to death | — |
Countries
France
Outcome results
None listed