A pilot study of a novel two-step approach for treating patients with brain cancer – treating the tumour blood vessels before activating the immune system
A Phase 1b/2 Study to Assess the Safety and Efficacy of Neoadjuvant Trametinib and Pembrolizumab in Patients with Newly Diagnosed Malignant Glioma
Sir Charles Gairdner Hospital
12 participants
Dec 1, 2025
Interventional
Conditions
Summary
This study will test a new treatment approach for brain cancer treatment before surgery, that involves giving two different drugs - trametinib to target leaky blood vessels within a brain tumour and an immunotherapy drug (pembrolizumab) that aims to activate the immune system. Who is it for? You may be eligible for this study if you are an adult, aged 18 years or older, you have been diagnosed with a malignant glioma (brain tumour) and you have not yet received any treatment for your cancer in the form of surgery, chemotherapy, radiotherapy, immunotherapy and ideally have not received prolonged steroids. Study details Participants who choose to enrol in this study will be assigned to either the intervention group or the standard treatment/control group by the study doctor. Participants who are assigned to the intervention group will be asked to take trametinib tablets daily for two weeks, and have an infusion of pembrolizumab prior to undergoing surgery to remove their tumour. Participants who are assigned to the standard treatment/control group will be asked to take dexamethasone tablets daily prior to undergoing surgery to remove their tumour. All participants will be asked to undergo an MRI scan prior to their surgery and within 48 hours of their surgery to assess the effect of each treatment on their brain. It is hoped this research will demonstrate that combined trametinib and pembrolizumab treatment prior to surgery to remove a brain tumour is safe, able to normalise blood vessels in the brain and increase the activity of the immune system to fight the cancerous cells. If this study is successful, a larger trial involving a greater number of brain cancer patients may go ahead.
Eligibility
Inclusion Criteria24
- Disease Characteristics
- Radiologically-diagnosed malignant glioma on MRI as diagnosed by a consultant diagnostic neuroradiologist.
- Supratentorial disease suitable for surgical resection.
- Unifocal disease.
- No infratentorial or intraventricular tumour visible on MRI.
- A CT chest, abdomen and pelvis showing no systemic malignancy.
- No history of systemic lymphoma.
- Patients should be treatment naïve having not undergone surgical resection or received chemotherapy or radiotherapy.
- Platelet count greater than 100,000 per microlitre.
- Absolute neutrophil count greater than 1000 per microlitre.
- Lymphocytes greater than 500 per microlitre..
- Hepatic
- Total bilirubin no greater than the upper limit of normal.
- AST and ALT no greater than twice the upper limit of normal.
- PT and APTT no greater than control.
- Negative hepatitis serology.
- Renal
- Creatinine within normal limits for age and sex.
- Other
- No medical condition that would preclude general anaesthesia.
- No severe acute infection.
- Not pregnant or nursing.
- Negative pregnancy test if appropriate.
- No documented allergy to trametinib or pembrolizumab.
Exclusion Criteria9
- Radiological suspicion of a diagnosis of brain abscess or metastasis.
- Radiological evidence of systemic malignancy.
- History of lymphoma.
- Patients requiring urgent surgery within 4 weeks.
- T1 contrast-enhancing disease on MRI that cannot be completely resected.
- Previous surgical treatment, chemotherapy or radiotherapy for their malignant glioma.
- Documented allergy to trametinib or pembrolizumab,
- Pregnancy.
- Severe hepatic impairment.
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Interventions
Patients with a new radiological diagnosis of malignant glioma will receive trametinib for 2 weeks followed by a single neo-adjuvant infusion of 200mg of pembrolizumab. Trametinib will be administed at escalating doses to 3 cohorts of 3 patients. The first cohort will receive 0.5mg daily for 2 weeks. Subject to dose-limiting toxicity not being observed in this patient cohort, the next cohort will receive 1mg daily for 2 weeks. If dose-limiting toxicity is not observed in this group, the last cohort will receive 2mg of trametinib daily. Control patients will undergo standard treatment. Controls will be recruited prior to study commencement and from patients, who have been offered enrolment in the treatment group, but who have declined and are happy to provide control tumour tissue. Upon completion of the course of trametinib they will undergo an MRI scan. Patients will then undergo surgical resection of their tumour. Tissue and pre-operative MRI scans will be compared to control patients, who have undergone standard treatment with dexamethasone.
Locations(1)
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ACTRN12625001269426