RecruitingPhase 2NCT07263438

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

Open-label Phase II Clinical Trial to Test the Efficacy of the Combination of Trimipramine and Atezolizumab With Bevacizumab in Patients With Recurrent Glioblastoma

Sponsor

Centre Hospitalier Universitaire Vaudois

Enrollment

59 participants

Start Date

Nov 3, 2025

Study Type

INTERVENTIONAL

Conditions

Glioblastoma Recurrence Tumor

Summary

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.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This Phase 2 study is testing whether adding trimipramine (an antidepressant with anti-tumor properties) to atezolizumab plus bevacizumab (an immunotherapy and anti-angiogenesis combination) can help treat glioblastoma — the most aggressive type of brain cancer — that has returned after standard treatment. **You may be eligible if...** - You have a confirmed diagnosis of glioblastoma that has come back for the first time after standard chemoradiotherapy (radiation plus temozolomide) - It has been at least 3 months since your initial combined radiation and chemotherapy - Your steroid dose has been stable or decreasing for at least 7 days before your baseline MRI - You are on no more than 4 mg of dexamethasone (or equivalent) at the time of enrollment **You may NOT be eligible if...** - You have had more than one recurrence of glioblastoma - You are on high doses of steroids - You have had recent surgery or invasive procedures - You have significant heart, liver, or immune system problems Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

DRUGTrimipramine

Trimipramine: daily oral intake at 75mg/ day for 7 days, then at 150 mg/ day

BIOLOGICALCohort 1: Atezolizumab

Atezolizumab: intravenous administration at 1200 mg on the first day of 3-week cycles.

BIOLOGICALBevacizumab

Bevacizumab will be administered intravenously at 15 mg/kg on the first day of 3-week cycles.

BIOLOGICALCohort 2: Atezolizumab

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.

BIOLOGICALCohort 2: Bevacizumab

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.