Senicapoc and Perampanel for Newly Diagnosed Glioblastoma

NCT07284069 | Recruiting Early Phase 1 DMC

• 1 other identifier: 2025-522605-37-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma

Keywords

glioblastoma; senicapoc; perampanel; early-phase; cancer neuroscience; neuro-oncology; window-of-opportunity trial; pacemaker cells

Outcome Measures

Primary Outcomes (2)

• Maximum tolerable dose of senicapoc monotherapy (mg)

  The primary endpoint of the study's Part A will be the maximum tolerable dose of senicapoc monotherapy (milligrams, first four weeks) when added to standard-of-care therapy.

  First four weeks of treatment

• Number of patients in each group (2 and 3) excluded from the study due to intolerability when exposed to perampanel at the lowest dose (2 mg)

  The primary endpoint of Part B is the number of patients in each group (2 and 3) excluded from the study due to intolerability when exposed to perampanel at the lowest dose (2 mg) within the first 6 weeks of treatment.

  First six weeks of treatment

Secondary Outcomes (6)

• Incidence and severity of adverse events

  From inclusion until 30 days after treatment completion (approximately 150 days total).

• Overall survival

  From randomization until death from any cause or End-of-trial (defined as 1 year after the last patient completes treatment in Part B), with an estimated maximum follow-up of approximately 24 months.

• Progression-free survival

  From randomization until first documented disease progression, death from any cause, or End-of-trial (defined as 1 year after the last patient completes treatment in Part B), with an estimated maximum follow-up of approximately 24 months.

• Objective response rate

  From postoperative baseline MRI until documented disease progression or End-of-trial (defined as 1 year after the last patient completes treatment in Part B), with an estimated maximum follow-up of approximately 24 months.

• Tumor volume

  From postoperative baseline MRI (<48h) until radiological progression, death, or End-of-trial (1 year after last patient completes Part B), with an estimated maximum follow-up of ~24 months.

Other Outcomes (14)

• Peak plasma concentration (Cmax) of senicapoc

  From Day 0 to ~30 days after last study-drug dose (blood samples at enrollment on Day 0, Days 12-14, Day 14, Days 14-16, Days 35-42, Days 90-100, Days 120-130, and up to 30 days post-treatment).

• Peak plasma concentration (Cmax) of perampanel

  From Day 0 to ~30 days after last study-drug dose (blood samples at enrollment on Day 0, Days 1-3, Days 12-14, Day 14, Days 14-16, Days 35-42, Days 90-100, Days 120-130, and up to 30 days post-treatment).

• Area under the plasma concentration-time curve (AUC) of senicapoc

  From Day 0 to ~30 days after last study-drug dose (blood samples at enrollment on Day 0, Days 1-3, Days 12-14, Day 14, Days 14-16, Days 35-42, Days 90-100, Days 120-130, and up to 30 days post-treatment).

Study Arms (3)

Senicapoc monotherapy (Group 1)

ACTIVE COMPARATOR

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).

Drug: senicapoc

Perampanel monotherapy (Group 2)

ACTIVE COMPARATOR

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.

Drug: Perampanel

Senicapoc and perampanel combination therapy (Group 3)

ACTIVE COMPARATOR

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.

Drug: senicapoc; Drug: Perampanel

Interventions

senicapoc DRUG

Senicapoc (ICA-17043) is a selective blocker of the intermediate-conductance calcium-activated potassium channel KCa3.1.

Senicapoc and perampanel combination therapy (Group 3); Senicapoc monotherapy (Group 1)

Perampanel DRUG

Perampanel (Fycompa®) is a non-competitive AMPA-receptor antagonist approved for the treatment of focal and generalized tonic-clonic seizures.

Perampanel monotherapy (Group 2); Senicapoc and perampanel combination therapy (Group 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• 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
• Eligibility for surgical resection and planned postoperative concomitant radiochemotherapy and adjuvant chemotherapy according to the Stupp regimen
• Eligible for safe postponement of surgery for 14 days from enrollment
• Life expectancy \> 3 months
• WHO Performance Status ≤ 2.
• Ability to provide written informed consent.
• Use of validated anti-conception for fertile female participants in concordance with guidelines provided by the Danish health and medicines authority.
• Signed written consent form.

You may not qualify if:

• Pregnancy or nursing. Fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy.
• Previous treatment with or allergic reaction to perampanel or senicapoc.
• Contraindications for senicapoc or perampanel treatment.
• Concomitant intake of enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbotal, or primidon).
• Significant co-morbidities, i.e.
• Significant liver function impairment (ALAT \> 210 umol/L for men and \> 135 umol/L for women or total bilirubin \> 25 umol/L)
• Significant renal impairment (eGFR \< 60 mL)
• Coagulopathy (INR \> 1.8 or APTT \> 57s)
• Thrombocytopenia (platelet count \< 100 x 103/μL = 100 x 109/L)
• Neutropenia (ANC \< 1.5 x 103/μL = 1.5 x 109/L)
• Anemia (Hb \< 10 g/L = 6.0 mmol/l)
• Severe cognitive impairment.
• Active participation in another therapeutic interventional clinical trial.
• 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.).

Sponsors & Collaborators

• Aarhus University Hospital: lead
• University of Aarhus: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Aarhus University Hospital, Department of Neurosurgery

Aarhus, Denmark, 8200, Denmark

RECRUITING

Related Publications (1)

• Pan C, Winkler F. Insights and opportunities at the crossroads of cancer and neuroscience. Nat Cell Biol. 2022 Oct;24(10):1454-1460. doi: 10.1038/s41556-022-00978-w. Epub 2022 Sep 12.

  PMID: 36097070 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

senicapoc; perampanel

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Anders R Korshoej, MD, PhD, Associate professor

CONTACT

(+45) 78450000; andekors@rm.dk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study consists of two parts enrolling a total of 27-36 patients: Part A is an initial dose-escalation phase (3+3 design) to determine the maximum tolerated dose of senicapoc when added to standard-of-care therapy. Following completion of Part A, Part B is conducted as a randomized, parallel-group phase in which patients are assigned 1:1 to receive standard-of-care therapy plus perampanel monotherapy or standard-of-care therapy plus the combination of perampanel and senicapoc at the established maximum tolerated dose.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 16, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 4, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Individual participant data (IPD) and supporting documents (study protocol, statistical analysis plan, and clinical study report) will be made available after publication of the primary trial results. Data will be accessible within 12 months following publication and will remain available for at least 5 years thereafter through an open-access repository (e.g., Zenodo.org) in accordance with FAIR data principles. Access to additional de-identified participant data may be granted upon reasonable request to the sponsor, in compliance with GDPR and Danish data protection law.
• Access Criteria: De-identified individual participant data (IPD) and supporting documentation (study protocol, statistical analysis plan, and clinical study report) will be available to qualified researchers following publication of the primary trial results. Data will be accessible through an open-access repository (e.g., Zenodo.org) in accordance with FAIR principles. Additional de-identified participant-level data may be shared upon reasonable written request to the sponsor, subject to approval and in compliance with applicable data protection regulations (GDPR) and Danish law.

Locations

DK (1)