A multicenter randomized phase 2 study to compare the efficacy and safety of avelumab versus standard second line treatment, in patients with metastatic colorectal cancer (MMR) after first line treatment progression.
- Conditions
- COLORECTAL METASTATIC CANCER WITH MICROSATELLITE INSTABILITY (MSI)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004575-49-FR
- Lead Sponsor
- Federation Francophone de Cancerologie Digestive
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 118
-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 < 3 months
-Patient failure (progression or unacceptable toxicity) of chemotherapy containing fluoropyrimidine (capecitabine or 5FU) +/- irinotecan +/- oxaliplatin with or without cetuximab, bevacizumab and panitumumab (patients in progression during or within 3 months after discontinuation of adjuvant chemotherapy are eligible)
-PNN > 1500/mm3, platelets > 100 000/mm3, Hb > 9 g/dL
-Total bilirubin < 25 µmol/L, ASAT < 5x LSN, ALAT < 5 x LSN, PT > 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
-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 < or = to the equivalent of 10 mg of prednisone daily, administration of steroids by a route resulting in minimal systemic exposure (local, intra-anal, intraocular or inhalation) are eligible).
-Transplant patients (including stem cell transplants), HIV positive or other immune deficiency syndromes
-Active infection by HBV or HCV
-Known severe hypersensitivity to monoclonal antibodies or history of anaphylactic shock, or uncontrolled asthma
-Any known specific contraindication or allergy to the treatments used in the study
-Persistence of toxicities related to 1st line chemotherapy grade > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method