A Phase 2 Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Silevertinib, an Oral EGFR Inhibitor, in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma With Unmethylated MGMT Promoter and EGFRvIII
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 162
- 试验地点
- 30
- 主要终点
- Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting.
Specifically, this study is being done to find answers to the following questions:
- How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM?
- What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)?
- Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?
详细描述
Silevertinib was designed to block a growth signal important to some cancers where tumors grow because of changes in a protein called epidermal growth factor receptor (EGFR). These changes are called gene amplifications, mutations, or alterations and are found in tumors. Temozolomide is a drug that fights cancer cells by damaging DNA (the genetic material of cells), which could cause the tumor cells to die. It is the standard treatment for adults with certain types of newly diagnosed brain cancer, like GBM. It is given together with radiotherapy and sometimes afterward as maintenance therapy.
This study has 2 parts. To be eligible for the study, participants must have received a diagnosis of GBM, had surgery to remove or reduce the size of the tumor, and received adjuvant radiation therapy and temozolomide. No other prior treatments for GBM are allowed.
In Part 1 (called the Safety Lead-in), participants will receive silevertinib combined with temozolomide to determine if the combination is safe and to find the best dose. Approximately 12 participants are expected to enroll in Part 1 of the study.
In Part 2, all participants will be randomized to one of two different treatment groups:
- Group 1: Silevertinib + temozolomide
- Group 2: Temozolomide only
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
- •Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
- •Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
- •For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
- •For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
- •For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
- •No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
- •At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
排除标准
- •Recurrent multifocal disease, metastatic, leptomeningeal, or extracranial GBM, or gliomatosis cerebri.
- •Progression of GBM prior to Enrollment, Screening, or Randomization.
- •Biopsy-only/no resectional surgery.
- •Prior or concomitant treatment for GBM with an EGFR-targeting agent, including silevertinib, bevacizumab, cytotoxic chemotherapy, immunotherapy, experimental therapies, Gliadel wafers, GammaTile®, or other intratumoral or intracavitary antineoplastic therapy.
- •Intent to use Optune® (TTF).
- •Significant other uncontrolled health conditions or other malignancies.
研究组 & 干预措施
temozolomide
temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
干预措施: temozolomide (TMZ) (Drug)
silevertinib and temozolomide
silevertinib at dose determined in Part 1 until disease progression in combination with temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
干预措施: silevertinib in combination with temozolomide (Drug)
结局指标
主要结局
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
时间窗: 12 months
Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.
次要结局
- Overall Survival(18 months)