Senicapoc and Perampanel for Newly Diagnosed Glioblastoma (SENIPERA)

Aarhus University Hospital

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Glioblastoma

Treatments: Drug: Perampanel; Drug: senicapoc

Study type: Interventional

Funder types: Other

Identifiers

NCT07284069

2025-522605-37-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

Glioblastoma is the most common and aggressive form of brain cancer in adults. Despite surgery, radiotherapy, and chemotherapy, most patients only live about one year after diagnosis. There is an urgent need for new and better treatments.

Recent research has shown that glioblastoma cancer cells communicate with surrounding brain cells through electrical signals that help the tumor grow and resist treatment. Two existing drugs, perampanel (used for epilepsy) and senicapoc (previously tested for blood disorders), may block these harmful signals. Laboratory studies suggest that combining these two drugs could slow tumor growth and make cancer cells more sensitive to standard therapy.

The SENIPERA trial will test whether perampanel and senicapoc, alone and in combination, are safe and well tolerated when added to standard treatment for newly diagnosed glioblastoma. The study will also measure how well these drugs reach the brain and tumor, and how they affect tumor biology.

The study has two parts:

Part A: Tests different doses of senicapoc alone to find the maximum tolerable dose.

Part B: Randomly assigns patients to receive either perampanel alone or perampanel together with senicapoc.

Participants will all receive standard therapy, including surgery, radiochemotherapy, and adjuvant chemotherapy. During surgery, small samples of tumor and fluid will be collected safely to study how the drugs act in the body and how tumor cells respond. Participants will be closely monitored for side effects and followed with regular clinical visits and MRI scans.

The trial will take place at Aarhus University Hospital, Denmark, from February 2026 to November 2028 and will enroll 27-36 adult patients. The study aims to identify safe and biologically active treatment combinations that could be tested in larger trials to improve future glioblastoma care.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

Senicapoc monotherapy (Group 1)

Active Comparator group

Description:

Dose escalation will follow a conventional 3 + 3 design to establish the maximum tolerated dose of senicapoc monotherapy, starting at the lowest dose level (DL 1) and proceeding stepwise according to observed dose-limiting toxicities. The maximum tolerable dose is defined as the highest dose level at which fewer than two of six patients experience a dose-limiting toxicity during the first four weeks of treatment. Senicapoc will be administered orally twice daily from the day of inclusion (Days 1-2) and continued until 30 days after completion of radiochemotherapy (approximately day 120-130).

Treatment:

Drug: senicapoc

Perampanel monotherapy (Group 2)

Active Comparator group

Description:

Perampanel dose-escalation will begin at 2 mg once daily and increase by 2 mg per week up to a maximum of 10 mg/day, depending on individual tolerability.

Treatment:

Drug: Perampanel

Senicapoc and perampanel combination therapy (Group 3)

Active Comparator group

Description:

Patients will receive senicapoc at the maximum tolerable dose defined in Group 1 in Part A, together with perampanel titrated as described for Group 2.

Treatment:

Drug: senicapoc

Drug: Perampanel