Efficacy of the Combination of Trimipramine and Atezolizumab With Bevacizumab in Patients With Recurrent Glioblastoma: a Phase 2 Trial

Sponsor
Centre Hospitalier Universitaire Vaudois
Study ID
NCT07263438
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Trimipramine — DRUG
    Trimipramine: daily oral intake at 75mg/ day for 7 days, then at 150 mg/ day
  • Cohort 1: Atezolizumab — BIOLOGICAL
    Atezolizumab: intravenous administration at 1200 mg on the first day of 3-week cycles.
  • Bevacizumab — BIOLOGICAL
    Bevacizumab will be administered intravenously at 15 mg/kg on the first day of 3-week cycles.
  • Cohort 2: Atezolizumab — BIOLOGICAL
    Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on the first day of 3-week cycles. Administration will occur once, then will be interrupted during a recovery period of 14-days post surgery, and then resumed.
  • Cohort 2: Bevacizumab — BIOLOGICAL
    Bevacizumab will be administered intravenously at 15 mg/kg on the first day of 3-week cycles. The first administration will take place 5 weeks after surgery.

Study Details

This is a multicentric phase II open-label clinical trial aiming to assess the efficacy of the combination of trimipramine and atezolizumab with bevacizumab in patients with recurrent glioblastoma. Eligible patients will be assigned to two cohorts depending on whether there is a medical indication for a neurosurgical resection from first recurrent tumor or not. The aim of the cohort 1 (patients without indication for surgery) is to analyze the clinical efficacy of this triple combination in recurrent glioblastoma. 48 patients will be registered. The aim of cohort 2 (patients with indication for surgery) is to confirm the level of trimipramine that can be achieved in the tumor tissue and cerebrospinal fluid collected during surgery. At least 5 patients will be registered. All patients will receive the combination treatment (trimipramine and atezolizumab associated with bevacizumab) for a maximum period of 2 years from registration. The treatment schedule is slightly different for the 2 cohorts because of the neurosurgical resection foreseen for cohort 2 and the requirement to start bevacizumab only after the surgery. After the end of treatment, all patients will be followed up for safety during 90 days from first treatment administration and then up to 3 years from registration.

Key Dates

Start date
Nov 3, 2025
Status verified
Feb 2026
Primary completion
Mar 30, 2028
Completion
Dec 31, 2030

Study Design

Enrollment
59 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1: Recurrent GBM without indication for re-resection
    Eligible patients will receive: trimipramine, bevacizumab and atezolizumab. Trimipramine will be taken orally daily (75 mg the first week and thereafter 150 mg), bevacizumab (15 mg/kg) and atezolizumab (1200 mg) will be administered intravenously every 3 weeks. Maximum treatment duration is 2 years. Patients will undergo clinical examination, vital signs measurements, and clinical laboratory evaluations regularly. Safety events will be collected up to 90 days after treatment end. Neurological assessment, quality of life assessment, brain Magnetic Resonance Imaging \[MRI\] and radiological assessment with Response Assessment in Neuro-Oncology \[RANO\] scale as per local guidelines will be performed every 9 weeks during study treatment administrations. Thereafter, these assessments will be performed every 12 weeks until clinical or radiological recurrence, for up to 3 years after registration.
  • Experimental: Cohort 2: recurrent GBm with an indication for re-resection
    Eligible patients will receive: Trimipramine taken orally daily (75 mg the first week and thereafter 150 mg) and atezolizumab (1200 mg) administered intravenously. Neurosurgical resection from first recurrent tumor will be planned 1 cycle after trial treatment start. Trimipramine will be continued during surgery and recovery period (minimum 2 weeks). Atezolizumab will be re-started after a minimum recovery period of 14 days after surgery at a fixed dose of 1200 mg administered intravenously, every 3 weeks. Bevacizumab will be started one cycle after the re-start of atezolizumab, at least 35 days after surgery. It will be administered intravenously at a dose of 15 mg/kg every 3 weeks for a maximum of 32 cycles of 21 days. Patients will undergo clinical and safety follow-up up to 3 years post-registration as for Cohort 1.

Primary Outcome Measure

Cohort 1: Progression-free survival rate [PFSR] [ Time Frame: 6 months after last patient's registration ]

Central Contacts

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