Adults with recurrent IDH mutated high grade gliomas (IDHm HGGs) MedDRA version: 20.0 Level: PT Classification code 10018338 Term: Glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Opdivo
Product Name: Opdivo
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: nivolumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type:
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological confirmation of grade III or IV high-grade glioma 2. Tumor is mutated for IDH1 or IDH2 gene (detected by R132HIDH immunochemistry or IDH1/IDH2 sequencing) 3. Age between 18 and 85 years old 4. Recurrence after radiotherapy and at least one line of alkylating chemotherapy (Temozolomide or PCV (Procarbazine, CCNU, Vincristine) (Surgery at recurrence is allowed before trial inclusion) 5. Recurrence occurring more than 12 weeks from the end of the radiotherapy or occurring outside the irradiated volume 6. Karnofsky performance status > 50 7. Radiologically measurable disease based on RANO criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions 8. Patients must be able to taper steroids (preferably discontinued). Dose at inclusion must be or = 2000/microL - Neutrophils > or = 1500/microL - Platelets > or = 100 x10^3/microL - Hemoglobin > 9.0 g/dL - Serum creatinine or = 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 1.04 / serum creatinine in µmol/l Male CrCl = (140 - age in years) x weight in kg x 1.23 / serum creatinine in µmol/l - AST/ALT =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding women 2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results 3. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways 4. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol 5. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or congestive cardiac insufficiency 6. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus and a known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 7. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or > 1.5 mg dexamethasone or equivalent*) or other immunosuppressive medications within 14 days of first study treatment administration. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone or > 1.5 mg dexamethasone or equivalent, are permitted in the absence of active autoimmune disease. 8. Any chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosourea) before the first dose of study treatment, 9. Receiving any other investigational agent or study drugs from a previous clinical study within 4 weeks before the first dose of study treatment (6 weeks for nitrosoureas). 10. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 11. History of allergy or Hypersensitivity to Nivolumab or to any of the excipients 12. Any unresolved toxicities (excepted alopecia), from prior therapy greater than CTCAE grade 1 at the time of inclusion. 13. Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur) or any other study drug component. 14. Surgical procedure < 7 days prior to first study treatment administration, vascular access device no restriction; 15. Subjects unable (e.g., due to pacemaker or ICD device) or unwilling to have a contrast-enhanced MRI of the head; 16. Known allergy or contraindication to Gadolinium; 17. Patients under guardianship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Nivolumab, based on 24 weeks progression-free survival (PFS24w) rate as assessed by RANO criteria in patients with recurrent IDHm HGGs;Secondary Objective: - To evaluate 24 weeks progression-free survival rate assessed by iRANO criteria - To evaluate median progression-free survival (median-PFS) assessed by RANO criteria - To evaluate median progression free survival (median-PFS) assessed by iRANO criteria - To evaluate overall survival (OS) - To evaluate overall response rate (ORR) assessed by RANO criteria - To evaluate overall response rate (ORR) assessed by iRANO criteria - To evaluate duration of response assessed by RANO criteria - To evaluate duration of response assessed by iRANO criteria - To evaluate longitudinal changes in quality of life (EORTC QLQ-C30 and BN20) - To evaluate the safety and tolerability of Nivolumab in patients with recurrent IDHm HGGs ;Primary end point(s): 6-months Progression-Free Survival (PFS) estimated by RANO criteria;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS24w rate documented using iRANO criteria - Median Progression-Free Survival (median-PFS) estimated by RANO and iRANO criteria - Overall survival (OS) defined as time from treatment initiation to death from any cause. - Overall response rate (ORR) estimated by RANO and iRANO criteria - Duration of response estimated by RANO and iRANO criteria - Longitudinal changes in quality of life (EORTC QLQ-C30 and BN20) - Safety: Type, frequency and severity of adverse events and serious adverse events will be graded according to the revised NCI Common Terminology Criteria V4.03 for Adverse Events (NCI CTCAE V4.03) ;Timepoint(s) of evaluation of this end point: 6 months and during all the participation of the patient | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed