Adding senicapoc and perampanel to standard treatment for newly diagnosed glioblastoma

Phase 0/1 Randomized Clinical Trial of SENIcapoc and PERAmpanel Mono- and Combination Therapy of Newly Diagnosed Glioblastoma

This trial will test whether giving the drugs perampanel and senicapoc, alone or together, with standard therapy is safe and reaches the brain in adults newly diagnosed with glioblastoma.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Aarhus (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Aarhus, Denmark)
• Trial ID: NCT07284069 on ClinicalTrials.gov

What this trial studies

This early-phase 1 trial adds the drugs perampanel and senicapoc to standard therapy for adults newly diagnosed with glioblastoma. Participants who are planned for surgical resection and the Stupp regimen may receive perampanel or senicapoc alone or both, given around the time of surgery and during standard chemoradiation. The study focuses on safety and tolerability, measures drug levels in blood and tumor to determine brain and tumor penetration, and examines effects on tumor biology. Initial dosing and combination tolerability will guide whether further trials are warranted.

Who should consider this trial

Good fit: Adults (18+) with newly diagnosed, presumed glioblastoma who are eligible for surgical resection and planned postoperative radiochemotherapy (Stupp regimen), have WHO performance status ≤2, and can safely delay surgery for up to 14 days.

Not a fit: Patients with recurrent glioblastoma, those who cannot undergo surgery or the Stupp regimen, pregnant or nursing individuals, or those with poor performance status are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, combining these drugs with standard therapy could slow tumor growth, make cancer cells more sensitive to treatment, and improve survival or quality of life.

How similar studies have performed: Blocking neuronal signaling in glioblastoma is a relatively new strategy supported by laboratory studies and clinical safety data for the individual drugs in other conditions, but there are no prior definitive clinical successes in glioblastoma.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older
2. Presumed GBM as determined by an expert multidisciplinary neuro-oncological tumor board, including participants from neurosurgery, neuro-oncology, neurology, and neuroradiology. The assessment should be based on a whole-brain MRI according to the consensus recommendations for a standardized brain tumor imaging protocol in clinical trials, not older than 4 weeks from the assessment
3. Eligibility for surgical resection and planned postoperative concomitant radiochemotherapy and adjuvant chemotherapy according to the Stupp regimen
4. Eligible for safe postponement of surgery for 14 days from enrollment
5. Life expectancy \> 3 months
6. WHO Performance Status ≤ 2.
7. Ability to provide written informed consent.
8. Use of validated anti-conception for fertile female participants in concordance with guidelines provided by the Danish health and medicines authority.
9. Signed written consent form.

Exclusion Criteria:

1. Pregnancy or nursing. Fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy.
2. Previous treatment with or allergic reaction to perampanel or senicapoc.
3. Contraindications for senicapoc or perampanel treatment.
4. Previous malignancy with completion of treatment within five years before inclusion, except for basal cell carcinoma.
5. Concomitant intake of enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbotal, or primidon).
6. Significant co-morbidities, i.e.

   1. Significant liver function impairment (ALAT \> 210 umol/L for men and \> 135 umol/L for women or total bilirubin \> 25 umol/L)
   2. Significant renal impairment (eGFR \< 60 mL)
   3. Coagulopathy (INR \> 1.8 or APTT \> 57s)
   4. Thrombocytopenia (platelet count \< 100 x 103/μL = 100 x 109/L)
   5. Neutropenia (ANC \< 1.5 x 103/μL = 1.5 x 109/L)
   6. Anemia (Hb \< 10 g/L = 6.0 mmol/l)
   7. Severe cognitive impairment.
7. Active participation in another therapeutic interventional clinical trial.
8. Any condition that might affect the absorption, distribution, metabolism, or excretion of the trial drugs (including malabsorption states as Whipple's disease, short bowel syndrome, etc.).

Where this trial is running

Aarhus, Denmark

• Aarhus University Hospital, Department of Neurosurgery — Aarhus, Denmark, Denmark (Recruiting)

Study contacts

• Study coordinator: Anders R Korshoej, MD, PhD, Associate professor

Conditions Glioblastoma; glioblastoma; senicapoc; perampanel; early-phase; cancer neuroscience; neuro-oncology; window-of-opportunity trial