A49 for Glioblastoma

Inclusion criteria

• {"criterion_text":"- Age between 18 and 75 years old\n- Free, informed and written consent signed\n- Histologically confirmed glioblastoma\n- Patients previously treated with concurrent radiotherapy (at least 45 Gy) with concomitant temozolomide, before the beginning of the 6 additional monthly cycles of temozolomide. Radiation therapy must have been completed 28 to 45 days prior to the first study treatment.\n- Karnofsky Performance Status ≥ 60%\n- Phase 1 only : Patients must be human leukocyte antigen (HLA)-A2 positive\n- Phase 1 only : PTPRZ1 expression in the tumor\n- Available tumor tissue for post hoc (retrospective) assessment of TERT promoter mutations and MGMT promoter methylation status\n- Life expectancy ≥ 3 months\n- Adequate organ function laboratory values within 15 days before initiation of treatment (see table in section 6.1)\n- Women or Male of childbearing potential (WOCBP) must use contraceptive methods during and for 180 days after the last dose of temozolomide or up to 120 days after the last dose of vaccine, whichever is longer (see section 6.3). No sperm donation during the study and until 7 months after the end of the treatment period.\n- Patient affiliated to the social security scheme"}

Exclusion criteria

• {"criterion_text":"- Known extracranial metastatic or leptomeningeal disease\n- Grade 4 astrocytoma IDH mutant\n- Steroid requirement >10 mg prednisone daily (or equivalent) at time of inclusion\n- Patients with prior malignancy active within the last 3 years\n- Patients receiving immunomodulatory or immunosuppressive therapy\n- Carmustine wafers (GliadelR) implantation during surgery\n- Phase 1 only: patient eligible and willing to be treated with Optune (TTF fields)\n- History of autoimmune disease (lupus, rheumatoid arthritis, inflammatory bowel disease...)\n- Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists\n- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study\n- Uncontrolled active systemic fungal, bacterial, viral, or other infection within the previous 4 weeks or requirement for intravenous (IV) antibiotics within the last two weeks\n- Breast-feeding or pregnant women\n- Contra-indications to MRI\n- Contra-indications to investigational medicinal product and/or to auxiliary medicinal products\n- Participation to another interventional clinical trial, clinical investigation or another interventional study or being in the exclusion period at the end of a previous study\n- Patient unable to follow the procedures and constraints of the protocol\n- Patient under legal protection (protection of the court, or in curatorship or guardianship)"}

Primary endpoints

• {"endpoint_text":"- Phase 1 : Safety. Safety AEs will be evaluated and graded according to CTCAE v5.0 a) clinically at D0, W2, W4, W6, M2, M3, M4, M5, M7, M9, M11 and M12 ; b) with blood samples at D0, W2, W4, W6, M2, M3, M5, M7, M9, M11 and M12 ; c) with cerebral MRI at baseline, M2, M3 and every 2 months thereafter. Phase 2a : immune efficacy: anti-TERT specific T cell responses in peripheral blood using IFN-gamma ELISPOT at 2 months post first immunizations.","definition_or_measurement_approach":"Phase 1: Safety assessed by AEs graded according to CTCAE v5.0, evaluated clinically at D0, W2, W4, W6, M2, M3, M4, M5, M7, M9, M11 and M12; blood samples collected at D0, W2, W4, W6, M2, M3, M5, M7, M9, M11 and M12; cerebral MRI at baseline, M2, M3 and every 2 months thereafter. Phase 2a: immune efficacy measured as anti-TERT specific T cell responses in peripheral blood using IFN-gamma ELISPOT at 2 months post first immunizations."}

Secondary endpoints

• {"endpoint_text":"- Evolution over time of anti-PTPRZ1 and anti-TERT immune T cell responses triggered by the vaccination protocol in peripheral blood using IFN-gamma ELISPOT before and during treatment (W2 for phase 1 only, W4, M2, M3, M5, M7, M9 and M12)","definition_or_measurement_approach":"Measured in peripheral blood by IFN-gamma ELISPOT at specified timepoints (W2 phase 1 only, W4, M2, M3, M5, M7, M9, M12)."}
• {"endpoint_text":"- Short and long-time safety, assessed clinically at D0, W2, W4, W6, M2, M3, M4, M5, M7, M9, M11 and M12 and with blood samples at D0, W2, W4, W6, M2, M3, M5, M7, M9, M11 and M12","definition_or_measurement_approach":"Clinical safety assessments at listed visits and laboratory assessments on blood samples at listed visits; AEs graded per CTCAE v5.0."}
• {"endpoint_text":"- Progression free survival with cerebral MRI at baseline, M2, M3 and every 2 months thereafter","definition_or_measurement_approach":"PFS assessed by cerebral MRI at baseline, M2, M3 and then every 2 months using RANO 2.0 criteria."}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"Overall survival measured from enrollment to death (no additional measurement details provided)."}
• {"endpoint_text":"- Quality of life by EORTC QLQ30 and BN20 questionnaires at baseline and at 5 months","definition_or_measurement_approach":"QoL assessed using EORTC QLQ-C30 and BN20 questionnaires at baseline and month 5."}
• {"endpoint_text":"- Cardiac safety in a cohort of 8 patients enrolled in the Phase 2a study assessed at D0 (pre injection and D0 + 3 hours), day 7, W2 and M2 and with blood samples at D0, W2 and M2","definition_or_measurement_approach":"Cardiac safety assessments at specified timepoints (D0 pre and D0+3h, day 7, W2, M2) and blood sampling at D0, W2, M2 in cohort of 8 patients."}
• {"endpoint_text":"- Circulating anti-melanin antibodies at baseline and M2 in a cohort of 8 patients enrolled in the Phase 2a","definition_or_measurement_approach":"Measurement of circulating anti-melanin antibodies at baseline and month 2 in a cohort of 8 phase 2a patients."}

France

Earliest CTIS Part Ii Submission Date

01-08-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

648

Number Of Sites

5

Number Of Participants

90

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France