Recurrent glioblastoma. MedDRA version: 19.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution fo
Sponsors
INSTITUT CLAUDIUS REGAUD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: INCLUSION CRITERIA: 1. Age = 18 years at time of study entry. 2. Previous Histopathologic confirmation of glioblastoma. 3. Any line of recurrence of glioblastoma proven by contrast enhanced MRI within 28 days prior to the first fraction of RT, per modified RANO criteria (Wen et al JCO 2010). Note: Recurrence is defined as progression following therapy (i.e., chemotherapy, radiation, second surgery). 4. Recurrent nodule of an histologically confirmed diagnosis of World Health Organization (WHO) Grade IV malignant glioma (Glioblastoma) occurring in or out the previous irradiation fields. 5. Recurrent disease documented by MRI evidence with a size of the recurrence evaluated on T1 post-gadolinium sequence =35mm. 6. Patient for which a re-irradiation (by hFSRT) has been decided by the multidisciplinary medical board. 7. Patients with measurable disease. 8. Prior radiotherapy must be ended at least 12 weeks before the first fraction of RT (unless progressive disease outside of the radiation field or histopathologic confirmation of unequivocal tumor to eliminate pseudoprogression images according to RANO recommendations, Wen et al JCO 2010). 9. In case of previous anti-VEGF/VEGFR targeted therapy: at least 28 days between the last injection of anti-VEGF/VEGFR targeted therapy and the first fraction of RT. 10. Karnofsky performance status =70. 11. Adequate hematologic, renal and hepatic function, as defined below: - Absolute Neutrophil Count = 1500/mm3 - Haemoglobin = 9.0 g/dL - Platelet count = 100,000/mm3 - Total bilirubin = 1.5 x ULN (for patient with confirmed Gilbert’s syndrome, Total bilirubin = 3 x ULN) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN - Creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min, using the Cockcroft-Gault formula: o Female CrCl = (140 - age in years) x weight in kg x 0.85 /72 x serum creatinine in mg/dL o Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL 12. Female Patients must either be of non-reproductive potential (i.e., post-menopausal by history: =60 years old and no menses for = 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. 13. Written informed consent and any locally required authorization (e.g., Social security for France (Health Insurance)) obtained from the patient prior performing any protocol-related procedures, including screening evaluations. 14. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 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 62 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA 1. Multifocal GBM recurrence. 2. Distance between tumor and optic ways including chiasma or brainstem 60 Gy for the primo-treatment for glioblastoma. 22. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing highly effective method of birth control. 23. Any condition that, in the clinical judgment of the investigator, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk. 24. Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Phase I part: - To assess intracranial progression-free interval (both distant and local intracranial progression). - To assess the overall survival. - To assess the safety and tolerability of hFSRT combined with Anti-PD-L1. Phase II part: - To assess intracranial progression-free interval (both distant and local intracranial progression). - To assess immune-related intracranial progression-free interval (both distant and local intracranial progression) in the experimental arm. - To assess the overall survival. - To evaluate acute and late toxicities of hFSRT combined with Anti-PD-L1. - To study the quality of life. - To study the neurologic and neurocognitive functions.;Primary end point(s): PHASE I PART: The schema will be defined as safe if one patient or less (i.e. 0 or 1) among 6 present DLT. PHASE II PART: The primary endpoint of the phase II part of the study is the local control rate (i.e. local progression of the irradiated tumor on the MRI according to the RANO criteria) at 6 months post-randomization.;Timepoint(s) of evaluation of this end point: PHASE I PART: 1 month after the last radiotherapy fraction. PHASE II PART: 6 months post randomization;Main Objective: Phase I part: The primary objective is to evaluate the safety and tolerability of the combination of hypofractionated stereotactic radiation therapy and Durvalumab immunotherapy in recurrent glioblastoma. Phase II part: The main primary objective of the phase II part is to evaluate the local control at 6 months of the combination of hypofractionated stereotactic radiation therapy and Durvalumab immunotherapy versus hypofractionated stereotactic radiation therapy alone for recurrent glioblastoma. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PHASE I PART: - Intracranial progression-free interval is defined by the time from inclusion to local or distant (outside the re-irradiated volume) progression. Patients without progression at last follow-up news are censored at this date. - Overall survival is defined as the time from inclusion to death from any cause. Patients alive at last follow-up news are censored at this date. - Safety and tolerability will be evaluated using the NCI-CTCAE Version 4.03. - Quality of life will be evaluated using EORTC QLQ-C30 and BN-20 questionnaires. - Neurologic and neurocognitive functions will be evaluated using NANO scale and MoCA tests. PHASE II PART: - Intracranial progression-free interval is defined by the time from randomization to local or distant (outside the re-irradiated volume) progression according to RANO criteria. Patients without progression at last follow-up news are censored at this date. - Immune-related intracranial progression-free interval is defined by the time from randomization to local or distant (outside the re-irradiated volume) progression (based on iRANO; Okada et al, 2015). Patients without progression at last follow-up news are censored at this date. - Overall survival is defined as the time from randomization to death from any cause. Patients alive at last follow-up news are censored at this date. - Acute and late toxicities will be evaluated using the NCI-CTCAE Version 4.03. - Quality of life will be evaluated using EORTC QLQ-C30 and BN-20 questionnaires. - Neurologic and neurocognitive functions will be evaluated using NANO scale and MoCA tests. - Time to QoL deterioration is defined as the time interval between randomization and first decrease in QoL score greater or equal to 5 points. Patients without such a QoL decrease will be censored at last follow-up news or at initiation of a new therapeutic strategy. - Time to neurocognitive deterioration is defined as the time interval between randomization and first of 3 | — |
Countries
France
Contacts
Public ContactCoordinating Investigator
INSTITUT CLAUDIUS REGAUD
Outcome results
None listed