Metastatic colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: STIVARGA
Product Name: REGORAFENIB
Product Code: REGIRI ( Irinotecan+regorafenib)
Pharmaceutical Form: Cachet
CAS Number: 755037-03-7
Other descriptive name: REGORAFENIB
Trade Name: IRINO
Sponsors
Institut régional du Cancer de Montpellier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent obtained before any study specific procedures 2. Male or female = 18 years of age 3. Histological or cytological documentation of adenocarcinoma of the colon or rectum 4. Patients with metastatic colorectal cancer 5. Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti VEGF therapy and an anti EGFR therapy (for RAS wild-type tumors) 6. ECOG performance status =1 7. Life expectancy of at least 3 months 8. Patients with A/A CCND1 genotype of rs603965 CCND1 9. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:Amylase and lipase =1.5 x ULN, Total bilirubin = 1.5 x ULN, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 x ULN (= 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) = 2.5 x ULN (= 5.0 x ULN for patients with liver involvement for their cancer and/or have bone metastases), Platelet count = 100,000/mm3; Hemoglobin (Hb) = 9 g/dL; Absolute neutrophil count (ANC) = 1,500/ mm3. Transfusion to meet the inclusion criterion, Serum creatinine = 1.5 x ULN 10. International normalized ratio (INR) = 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) = 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care 11. Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment 12. Women of childbearing potential and men must agree to use adequate contraception before entering the study until at least 8 weeks after the last study drug administration of Regorafenib and 12 weeks after the last study drug administration of Irinotecan. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 312 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 312
Exclusion criteria
Exclusion criteria: 1. Patients with A/G or G/G CCND1 genotype of rs603965 CCND1 2. Prior treatment with regorafenib or sorafenib 3. Prior treatment with TAS 102 4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug 5. Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug 6. Congestive heart failure = New York Heart Association (NYHA) class 2 7. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) 8. Myocardial infarction less than 6 months before start of study drug 9. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) 10. Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) 11. Pleural effusion or ascites that causes respiratory compromise (= NCI-CTCAE V5.0 Grade 2 dyspnea) 12. Ongoing infection > Grade 2 NCI-CTCAE V5.0 13. Known history of human immunodeficiency virus (HIV) infection 14. Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy 15. Patients with seizure disorder requiring medication 16. History of organ allograft 17. Patients with evidence or history of any bleeding diathesis, irrespective of severity 18. Any hemorrhage or bleeding event = NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication 19. Non-healing wound, ulcer, or bone fracture 20. Dehydration NCI-CTCAE V5.0 Grade = 1 21. Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results 22. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 23. Any illness or medical conditions that are unstable or could jeopardize the safety of the subject and his/her compliance in the study 24. Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours) 25. Patients unable to swallow oral medications 26. Any malabsorption condition 27. Chronic inflammatory bowel disease and / or bowel obstruction 28. Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity = Grade 2 29. Concomitant participation or participation within the last 30 days in another clinical trial 30. Systemic anticancer therapy during this trial or within 4 weeks before randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of overall survival in the Regorafenib and REGIRI combination (Regorafenib + Irinotecan) arms in mCRC patients of Cyclin D1 A/A genotype. ;Secondary Objective: Study of: -Progression-free survival -Objective response rate -Disease control rate according to Recist criteria (version 1.1) -Toxicity (according to the NCI-CTCAE v5.0) -Quality of life (EORTC QLQ-C30) ;Primary end point(s): Overall survival presented with its median and confidence interval at 95%, estimated from randomization date to the date of death, whatever the cause, using the Kaplan-Meier method;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoint include: - Progression-free survival (PFS), defined as the time (days) from date of randomization to date of first observed disease progression (investigator’s radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented. Patients without tumor progression or death at the time of analysis will be censored at their last date of tumor assessment. - Disease control rate (DCR), defined as the rate of patients, whose best response was not progressive disease (i.e., CR, PR or SD), to all randomized patients in the treatment group - Objective response rate (OOR), defined as the rate of patients with CR or PR, to all randomized patients in the treatment group. Patients prematurely discontinuing without an assessment will be considered non-responders for the analysis. - Safety will be evaluated using the NCI-CTCAE version 5.0 scale; at each visit for the duration of the treatment. -Quality of life will be evaluated, using the EORTC QLQ-C30 questionnaire. The expected benefit is an overall survival improvement of this treatment in patients with metastatic colorectal cancer who have received all standard treatments except TAS-102 and Regorafenib. ;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Countries
France
Contacts
Public ContactDr Jean Pierre BLEUSE
Institut régional du Cancer de Montpellier
Outcome results
None listed