A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 主要终点
- Rate of Laboratory Abnormalities
研究概览
简要总结
This study aims to test the hypothesis that combining serabelisib, a PI3K alpha isoform inhibitor, with an SGLT2 inhibitor, canagliflozin will improve efficacy in the treatment of patients with advanced solid tumors.
详细描述
This study aims to test the hypothesis that controlling the glucose/insulin feedback will enhance the efficacy of PI3K inhibition in treating solid tumors. The treatment consists of serabelisib, a PI3K alpha isoform (PI3Kα) inhibitor, combined with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. The study will assess the safety and efficacy of the combination in adult patients with advanced solid tumors harboring mutations that may be dependent on PI3Kα activity: PIK3CA mutations and KRAS mutations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Have histologically or cytologically confirmed locally advanced or metastatic solid tumors.
- •Have a tumor harboring a mutation in PIK3CA or KRAS genes.
- •Have received prior therapy and have recurrent or persistent disease without standard therapies available, or are ineligible to receive standard therapies.
- •Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤2
- •Have adequate organ function.
- •Have adequate birth control during the course of the study.
- •Are able to receive canagliflozin
排除标准
- •Diagnosis of primary brain tumor
- •Untreated brain metastasis or history of leptomeningeal disease
- •Have received prior chemotherapy within 28 days or other anticancer agents within 28 days of 5 half lives (whichever is the shorter duration) before the first administration of study drug. The exception is patients in Cohort 4 (PIK3CA-mutated breast cancer) are allowed to receive ongoing endocrine therapy.
- •Have diabetes mellitus requiring insulin therapy
- •Have diabetes mellitus requiring insulin secretagogue therapy
- •Have poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) >7.5%
- •Have a secondary malignancy requiring therapy or are unstable without therapy.
- •Known impaired cardiac function or clinically significant cardiac disease.
- •Myocardial infarction or unstable angina within 6 months before the first administration of study drug.
- •Pregnant (positive serum pregnancy test) or breastfeeding
研究组 & 干预措施
Serabelisib
Part 1 is dose escalation of Serabelisib Cohort 1 = 600mg; Cohort 2 = 900mg; Cohort 3 = 1200mg
Part 2 is expansion of mutational cohorts with selected dose as follows:
Cohort 4 = PIK3CA-mutated breast cancer; Cohort 5 = PIK3CA-mutated Non breast cancer; Cohort 6 = KRAS mutated
干预措施: Serabelisib (Drug)
Serabelisib
Part 1 is dose escalation of Serabelisib Cohort 1 = 600mg; Cohort 2 = 900mg; Cohort 3 = 1200mg
Part 2 is expansion of mutational cohorts with selected dose as follows:
Cohort 4 = PIK3CA-mutated breast cancer; Cohort 5 = PIK3CA-mutated Non breast cancer; Cohort 6 = KRAS mutated
干预措施: Canagliflozin 300mg (Drug)
结局指标
主要结局
Rate of Laboratory Abnormalities
时间窗: 30 days after last dose
Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities
Dose confirmation
时间窗: 6 months
To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin
Rate of Adverse Events
时间窗: 30 days after last dose
Safety of serabelisib in combination with canagliflozin as evaluated by incidence of drug-related adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities.
Tumor Assessments by RESIST
时间窗: 2 years
To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations
次要结局
- AUC Pharmacokinetic assessment(Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours)
- Tmax Pharmacokinetic assessment(Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours)
- Cmax Pharmacokinetic assessment(Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours)