Phase 0/1 Randomized Clinical Trial of SENIcapoc and PERAmpanel Mono- and Combination Therapy of Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum tolerable dose of senicapoc monotherapy (mg)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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.
排除标准
- •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.
- •Previous malignancy with completion of treatment within five years before inclusion, except for basal cell carcinoma.
- •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.).
研究组 & 干预措施
Senicapoc monotherapy (Group 1)
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).
干预措施: senicapoc (Drug)
Perampanel monotherapy (Group 2)
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.
干预措施: Perampanel (Drug)
Senicapoc and perampanel combination therapy (Group 3)
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.
干预措施: senicapoc (Drug)
Senicapoc and perampanel combination therapy (Group 3)
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.
干预措施: Perampanel (Drug)
结局指标
主要结局
Maximum tolerable dose of senicapoc monotherapy (mg)
时间窗: First four weeks of treatment
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.
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)
时间窗: First six weeks of treatment
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.
次要结局
- 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.)
- Perampanel dose levels(First six weeks of treatment)