[Translation] A randomized, double-blind, placebo-controlled phase III trial evaluating Enzastaurin combined with temozolomide concurrent chemoradiotherapy plus adjuvant chemotherapy in patients with newly diagnosed glioblastoma and positive for the novel biomarker DGM1
主要目的:
在新诊断为胶质母细胞瘤的Denovo基因标记物1(DGM1)阳性患者中,与安慰剂对照,评估enzastaurin联合替莫唑胺同步放化疗加辅助化疗方案在患者总生存期(OS)方面的优效性。
次要目的:
1. 在DGM1生物标记物阳性患者中比较治疗组间的无进展生存期(PFS)。
2. 在DGM1生物标记物阳性患者中比较治疗组间的客观缓解率(ORR)。
3. 进一步评估enzastaurin加入替莫唑胺同步放化疗加辅助化疗方案后的安全性特征。
探索性目的:
1. 在DGM1生物标记物阴性患者中评估总生存期(OS)。
2. 确定色素尿的存在(尿液呈橙色/红色)是否与服用enzastaurin的患者生存期改善存在关联。
3. 分析尿液中是否存在enzastaurin和enzastaurin代谢产物(尿液药代动力学[PK])。
4. 评估其它胚系或肿瘤生物标记物的存在是否与服用enzastaurin的患者的疗效改善存在关联。
5. 确定enzastaurin和enzastaurin代谢产物的浓度,以便纳入后续的群体PK分析中。
[Translation] Primary Objectives:
To evaluate the superiority of enzastaurin in combination with concurrent chemoradiotherapy plus adjuvant chemotherapy with temozolomide compared with placebo in terms of overall survival (OS) in patients with newly diagnosed glioblastoma who are Denovo Genetic Signature 1 (DGM1) positive.
Secondary Objectives:
1. To compare progression-free survival (PFS) between treatment arms in patients who are DGM1 biomarker positive.
2. To compare objective response rate (ORR) between treatment arms in patients who are DGM1 biomarker positive.
3. To further evaluate the safety profile of enzastaurin added to concurrent chemoradiotherapy plus adjuvant chemotherapy with temozolomide.
Exploratory Objectives:
1. To evaluate overall survival (OS) in patients who are DGM1 biomarker negative.
2. To determine if the presence of pigmenturia (orange/red urine) is associated with improved survival in patients taking enzastaurin.
3. To analyze the presence of enzastaurin and enzastaurin metabolites in urine (urine pharmacokinetics [PK]).
4. Evaluate whether the presence of other germline or tumor biomarkers is associated with improved efficacy in patients taking enzastaurin.
5. Determine the concentrations of enzastaurin and enzastaurin metabolites for inclusion in subsequent population PK analyses.