NCT06388733进行中（未招募）3 期
A Phase 3, Open-label, Randomized 2-arm Study Comparing the Clinical Efficacy and Safety of Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
Ivy Brain Tumor Center160 个研究点 分布在 8 个国家目标入组 450 人开始时间: 2024年6月19日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 450
- 试验地点
- 160
- 主要终点
- Overall survival
研究概览
简要总结
The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main question it aims to answer is:
Does niraparib improve overall survival (OS) compared to TMZ?
Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ.
- study drug (Niraparib) or
- comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma).
The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks.
Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study.
Participants' tasks will include:
- Complete study visits as scheduled
- Complete a diary to record study medication
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
盲法说明
Blinded Independent Central Review is composed of independent radiologists and will be utilized to assess progression of disease
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
- •1. Histologic documentation of a newly-diagnosed intracranial GBM, per 2021 WHO classification guidelines through local pathology review.
- •2. Age ≥18 years at the time of signing informed consent.
- •3. Sufficient tissue available for retrospective central pathology review, retrospective central confirmation of MGMT promoter methylation status and genomic analysis. If insufficient tissue is available,pproval may be granted on a case-by-case basis after a review.
- •4. Unmethylated MGMT promoter region determined locally by a validated PSQ or qMS-PCR assay compliant to local regulations. Numerical cut-off for an MGMT unmethylated tumor will be defined in the protocol.
- •5. Suitability for SOC RT to 60 Gy in 30 fractions using ESTRO-EANO 'single phase' targeting approach [Niyazi, 2023], per investigator's judgment.
- •6. No prior treatment for GBM (including brachytherapy or BCNU wafers), other than surgical resection or biopsy.
- •7. Female participants: Not pregnant, planning to get pregnant, or breastfeeding and one of the following conditions apply: is of nonchildbearing potential or is of childbearing potential AND using a contraceptive method that is highly effective (with a failure rate of <1% per year) from screening through at least 180 days after the last dose of study intervention. Breastfeeding is contraindicated during the study and for one month after the last dose of study intervention.
- •8. Male participants: Must agree to the following during the study intervention period and for at least 6 months after the last dose of study intervention: refrain from donation sperm PLUS be abstinent from heterosexual activity or agree to use a male condom and be advised of the benefit for a female partner to use a contraceptive method that is highly effective (with a failure rate of <1% per year).
- •9. The participant must be capable of providing signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •10. Karnofsky performance status of ≥
- •11. Adequate organ function
- •12. Normal blood pressure (BP) or adequately treated and controlled hypertension (defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
- •13. Stable or decreased dose of dexamethasone, requiring no more than 5 mg daily equivalent dose, within 7 days before randomization.
- •14. Ability to swallow oral medications whole.
排除标准
- •1. Presence of metastatic or predominant leptomeningeal disease.
- •2. Current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
- •3. Participant is at an increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to start of study treatment with the exception of tumor resection).
- •4. Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
- •5. Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. NOTE: Stable noncirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones), hepatobiliary involvement of malignancy, or chronic stable HBV infection (in a participant for whom HDV infection has been excluded) or chronic HCV infection is acceptable if the participant otherwise meets entry criteria.
- •6. Known human immunodeficiency virus (HIV) unless participants meet all of the following criteria:
- •Cluster of differentiation 4 ≥350/µL and viral load <400 copies/mL.
- •No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment.
- •No history of HIV-associated malignancy for the past 5 years.
- •Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV [NIH, 2021] started >4 weeks prior to study enrollment.
- •7. MDS/AML or with features suggestive of MDS/AML.
- •8. History of another malignancy within 2 years prior to registration. Participants with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Participants with a history of other malignancies are eligible if they have been treated with curative intent or continuously disease free for at least 2 years after definitive primary treatment.
- •9. Prior history of posterior reversible encephalopathy syndrome (PRES).
- •10. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow-up procedures.
- •11. Inability to undergo MRI brain with IV contrast.
- •12. Biopsy and/or resection (whichever is later) occurring >6 weeks prior to planned RT start date.
- •13. Surgical wound complication recovery at the time of enrollment.
- •14. Known hypersensitivity to the components of niraparib, TMZ, or their formulation excipients.
- •15. Known hypersensitivity to dacarbazine (DTIC).
- •16. Prior therapy with PARP inhibitors for systemic cancer.
- •17. Received a live vaccine within 30 days before the planned start of study intervention. Coronavirus disease 2019 (COVID-19) vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
- •18. Received a transfusion (platelets or red blood cells) or colony-stimulating factors (e.g., granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks of the planned start of study intervention.
- •19. Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product.
- •20. Treatment with tumor treating fields (e.g., Optune) for GBM.
- •21. Presence of known isocitrate dehydrogenase (IDH) mutation.
- •22. Presence of known H3 mutation.
- •23. Previous diagnosis of WHO Grade 2 or 3 glioma.
研究组 & 干预措施
Arm B: Temozolomide
Active Comparator
干预措施: Temozolomide (Drug)
Arm A: Niraparib
Experimental
干预措施: Niraparib (Drug)
结局指标
主要结局
Overall survival
时间窗: 24 months
Overall survival, defined as the time from the date of randomization to the date of death due to any cause.
次要结局
- Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-C30-item Core module (EORTC QLQ-C30) (Scores on a scale)(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Overall response rate(24 months)
- Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-BN20-item Core module (EORTC QLQ-BN20) (Scores on a scale)(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Changes from baseline in neurocognitive function assessed by Controlled Oral Word Association(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Changes from baseline in neurocognitive function assessed by Trail Making Test Parts A and B(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Frequency and severity of symptomatic AEs based on PRO-CTCAE(24 months)
- Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)(24 months)
- Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EQ-5D-3L(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Changes from baseline in neurocognitive function assessed by Hopkins Verbal Learning test(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
- Incidence of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)(24 months)
- Incidence of treatment discontinuations, dose interruptions, and dose reductions due to AEs, SAEs, or AESIs, changes in Karnofsky performance status, changes in clinical laboratory results, and vital sign measurements(24 months)
研究者
研究点 (160)
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