COLORECTAL METASTATIC CANCER WITH MICROSATELLITE INSTABILITY (MSI)
Conditions
Interventions
Product Name: Anti PD-L1
Product Code: Avelumab
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: ELVORINE
Pharmaceutical Form: Solution for infusion
Other descriptive name: CALC
Sponsors
Federation Francophone de Cancerologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically proven colorectal adenocarcinoma with metastasis(es) non-resectable - MSI-H determined by immunohistochemistry (loss of expression of MLH1, MSH2, MSH6 and/or PMS2) or by molecular biology - At least one measurable target (primary tumor or metastasis) according to RECIST v1.1 - Mutational status RAS and BRAF - Age = 18 - OMS = 2 - Life expectancy 1500/mm3, platelets > 100 000/mm3, Hb > 9 g/dL - Total bilirubin 60%, - Creatinine clearance > 50 ml/min according to MDRD formula - Patient belonging to a social security scheme - Patient information and signature of the informed consent 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 78 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR - Patient treated with FOLFIRINOX or FOLFOXIRI in 1st line - Cerebral metastasis - Previous treatment with anti-PD1 or anti-PDL1 - Autoimmune disease that might be aggravated during treatment with an immuno-stimulating agent (patients with type I diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) - Immunosuppressive long-term treatment (patients necessitating a corticotherapy are eligible if they are administered in doses 2 (NCI-CTC v4.0) (except alopecia and neuropathy sequelae of oxaliplatin) - Vaccination during the 4 weeks preceding the start of treatment - Known deficit in DPD - QT/QTc interval > 450 msec for men and > 470 msec for women - K+ < LIN, Mg2+ < LIN, Ca2+ < LIN - Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack - Any progressive pathology not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure - Patient with interstitial pneumonitis or pulmonary fibrosis or any other known severe respiratory insuficiency - History of inflammatory bowel disease or unresolved occlusion or sub-occlusion in symptomatic treatment - History of malignant pathologies during the past 5 years except basocellular skin carcinoma or in situ cervical carcinoma, properly treated - Patient already included in another clinical trial during treatment with an experimental molecule for L2 or treatment ended in the last 4 weeks before inclusion - Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test - Persons deprived of liberty or under supervision - Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare between the two treatment arms (arm A: 2nd line chemotherapy, arm B: avelumab) progression-free survival by central review (RECIST 1.1 for Arm A and iRECIST for arm B) ;Secondary Objective: -Time to progression (RECIST and iRECIST) -Overall survival (median) -Time to best response (RECIST and iRECIST) -Response rate (RECIST and iRECIST) -Best response under treatment (RECIST and iRECIST) -Toxicity according to NCI-CTC v4.0 -Depth of response -Early tumor shrinkage 8 weeks -Secondary resection rate (R0 and R1) -Histological response in case of secondary resection (TRG criteria and mTRG) -Evolution of tumor markers (CEA) -Quality of life QLQ-C30 ;Primary end point(s): The primary endpoint is radiographic progression-free survival (PFS). The progression will be assessed by central review according to the criteria RECIST v1.1 in arm A and according to the criteria irRECIST in arm B. PFS is defined as the time between the date of randomization and the date of the first radiological progression or the date of death (for whatever reason). Patients living without radiological progression will be censured on the date of their latest x-ray. ;Timepoint(s) of evaluation of this end point: up to 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For all secondary endpoints, the radiological responses will be evaluated according to the criteria RECIST v1.1 in arm A and according to the criteria irRECIST in arm B in central review. A sensitivity analysis can be made by taking into account the radiological responses of the investigators. The secondary endpoints are: - Time To Progression (TTP): This is defined as the time between the date of randomization and the date of the first radiological progression. Patients living or dead without radiological progression will be censured on the date of their latest x-ray. - Overall survival (OS): Defined as the time between the date of randomization and the date of death (regardless of the cause). Living patients will be censured at the date of their latest news. - Response Rate : This is defined as patients with partial or complete response according RECIST 1.1 criteria. - Time to Best Response (TBR) This is defined as the time from the date of randomization and the date of best response under treatment. Patients without imaging (better response non-evaluable, untreated patients) will not be taken into account in the analysis. - The best response under treatment: The best tumor response will be evaluated throughout the treatment. It is described by the rate according to the various categories: complete, partial, stability, progression or non-evaluable response. - Toxicities: Toxicity will be evaluated according to NCI-CTC v4.0. - Early tumor shrinkage at 8 weeks: This is defined as the relative difference between the sum of the largest diameters of target lesions at 8 weeks and this sum at inclusion. Early decrease corresponds to a relative difference of > 20% and > 30% in iRECIST v1.1. - Depth of response: This is defined as the relative difference between the sum of the largest diameters of target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the tar | — |
Countries
France
Contacts
Public ContactBEZ Jérémie
Federation Francophone de Cancerologie Digestive
Outcome results
None listed