A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 38
- 试验地点
- 3
- 主要终点
- Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle
研究概览
简要总结
A phase Ib dose-escalation study of the AEB071 and MEK162 combination in adult patients with confirmed metastatic uveal melanoma. Cohorts of 3-6 patients will be assessed for dose limiting toxicities (DLTs) during Cycle 1 until the maximum tolerated dose (MTD) of the combination therapy is determined. The MTD or Phase 2 Recommended Dose (P2RD) will be used in a Phase II part of the study, which will enrol 55 patients each into two randomized groups: the combination therapy or MEK162 alone. The Phase II part will continue until proof of concept is established. Patients will continue treatment as long as clinical benefit is seen and no limiting adverse toxicity is observed
详细描述
Due to halted enrollment, the Phase II part of the study was not conducted. The Sponsor decided to permanently stop recruitment for the study prior to MTD determination.
Remaining patients on treatment with binimetinib and sotrastaurin who were considered by the Investigator to be benefiting from their treatment could have continued treatment and were to be followed up as per protocol. No patients were ongoing as of the data cut-off date. After the last patient last visit (LPLV) was declared, the study was terminated.
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
- •Written informed consent
- •Male and female patients aged 18 years or older
- •A history of uveal (ocular) melanoma with biopsy-confirmed metastatic disease
- •Consent to providing 3 tumor biopsy samples throughout the course of the study
- •Presence of measurable disease
- •A WHO performance status of less than or equal to 1
排除标准
- •Presence of CNS lesions (stable lesions may be acceptable)
- •Previous or concurrent malignancy, other than basal cell or squamous cell carcinoma of the skin: in situ carcinoma of the cervix, without evidence of recurrence for at least 3 years; a primary malignancy completely resected and no evidence of recurrence for at least 3 years
- •Adverse event from prior chemotherapy, radiotherapy or surgery that has not recovered to CTCAE v4.03 Grade 1 or less, except for alopecia/sensory peripheral neuropathy, which must be less than Grade 2
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
- •Impaired cardiac function or clinically significant cardiac disease
- •Impaired GI function or disease that could interfere with the absorption of AEB071 and/or MEK162
- •Treatment with medicines or herbal supplements that are known inhibitors or inducers of CYP3A4/5 and cannot be withdrawn prior to study treatment
- •Females of child-bearing potential who are unwilling or unable to use highly effective means of contraception
- •Males who are unwilling or unable to use a condom during sexual intercourse
- •Prior exposure to a MEK or PKC inhibitor Other inclusion/exclusion criteria apply
研究组 & 干预措施
Arm B
MEK162 alone
干预措施: MEK162 (Drug)
Arm A
AEB071 and MEK162 combined
干预措施: MEK162 (Drug)
Arm A
AEB071 and MEK162 combined
干预措施: AEB071 (Drug)
结局指标
主要结局
Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle
时间窗: Cycle 1 (up to 28 days)
A DLT is defined as an adverse event or abnormal laboratory value as defined in the protocol that is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with AEB071 and MEK162.
Phase II: Progression Free Survival (PFS)
时间窗: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
The time from date of randomization to the date of event defined as the first documented progression or death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination.
次要结局
- Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15)(Cycle 1 (Day 15))
- Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15)(Cycle 1 (Day 15))
- Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15)(Cycle 1 (Day 15))
- Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR)(Cycle 1 (up to 28 days))
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15)(Cycle 1 (Day 15))
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR)(Cycle 1 (up to 28 days))
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS)(Cycle 1 (up to 28 days))
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR)(From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit))
- Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15)(Cycle 1 (Day 15))
- Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1)(Cycle 1 (Day 1))
- Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15)(Cycle 1 (Day 15))