A Phase I/Ib Study for the Evaluation of SAR260301, Administered Orally in Monotherapy in Patients With Advanced Solid Tumors or Lymphomas, and in Combination With Vemurafenib in Patients With Unresectable / Metastatic BRAF-mutated Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Maximal tolerated dose (MTD) of SAR260301 in combination with vemurafenib (Study Part B)
研究概览
简要总结
Primary Objective:
Part A - Monotherapy:
- To determine the maximum tolerated dose (MTD) of SAR260301 administered as monotherapy and either on a once or twice daily schedule, to patients with advanced solid tumors or lymphomas.
Part B - Combination:
- To determine the maximum tolerated dose (MTD) of SAR260301 administered in combination with the recommended standard dosage of vemurafenib to patients with unresectable / metastatic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma.
Secondary Objectives:
- To characterize the overall safety and tolerability profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B).
- To characterize the pharmacokinetic (PK) profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B) as well as vemurafenib PK in combination with SAR260301 (Part B)
- To evaluate food effect on SAR260301 PK (Part A)
- To assess preliminary antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria).
- To assess preliminary antitumor activity using volumetric computed tomography (CT) or magnetic resonance imaging(MRI)
- To evaluate the pharmacodynamic (PD) effects of SAR260301 on blood and tumor.
- To evaluate PK/PD relationships.
- To identify the recommended phase 2 dose of SAR260301 in combination with vemurafenib (RP2D) (Part B only)
- To assess potential induction effect of SAR260301 on cytochrome P450 (CYP) isoenzyme 3A (CYP3A) (Part A)
详细描述
Study duration for one patient will include a period for inclusion (screening period) of up to 4 weeks, a treatment period of at least 4 weeks, and a end-of-study visit at 30 days following the last administration of study drug. The patient may continue treatment until disease progression, unacceptable toxicity or willingness to stop, followed by a minimum of 30-days follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A Monotherapy
Dose escalation of daily or twice daily SAR260301 within a 28-day cycle, followed by an expansion phase at the maximal tolerated dose
干预措施: SAR260301 (Drug)
Part B Combination
Dose escalation of twice-daily SAR260301 within a 28-day cycle and in combination with 720 or 960 mg twice daily of Vemurafenib, followed by an expansion phase at the maximal tolerated dose of SAR260301 in combination
干预措施: SAR260301 (Drug)
Part B Combination
Dose escalation of twice-daily SAR260301 within a 28-day cycle and in combination with 720 or 960 mg twice daily of Vemurafenib, followed by an expansion phase at the maximal tolerated dose of SAR260301 in combination
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Maximal tolerated dose (MTD) of SAR260301 in combination with vemurafenib (Study Part B)
时间窗: Day 28
Maximal tolerated dose (MTD) of SAR260301 in monotherapy (Study Part A)
时间窗: Day 28
次要结局
- Assessment of PK parameters for SAR260301 including tmax, Cmax, AUC fasting and fed (food effect)(Only part A)(Up to 8 weeks)
- Assessment of urine excretion of SAR2690301 (Part A)(12-24 hours at Day 28)
- Assessment of PD parameter AKT phosphorylation in tumor (expansion phase only)(15 days)
- Assessment of PK parameters for SAR260301 and vemurafenib, including tmax, Cmax, AUC, Rac (Day 28/Day1), half-life, CL, Ctrough(4 weeks)
- Assessment of potential for CYP induction (4beta-hydroxycholesterol)(Part A)(Up to 15 days)
- Assessment of PK parameter Rac (Day 28/Day 1) on AUC and Cmax(4 weeks)
- Assessment of PD parameter Serine/threonine protein kinase Akt (AKT) phosphorylation in blood platelets(4 weeks)
- Number of patients with treatment emergent events(Up to 2 years)
- Assessment of preliminary antitumor activity as documented by tumor response (defined by RECIST1.1 criteria for solid tumors, international working group (IWG) and revised response for lymphomas, and tumor markers when relevant)(Up to 2 years)