A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 41
- 试验地点
- 3
- 主要终点
- Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
研究概览
简要总结
This is a phase I/II trial to evaluate the efficacy of APG-115 +/- Carboplatin for the treatment p53 wild-type malignant salivary gland cancer.
Part 1 consisted of 2 arms, arm A (APG-115 monotherapy) and arm B (APG-115 + Carboplatin) and was terminated early.
Part 2 is a single arm study (APG-115 monotherapy).
详细描述
The current single arm study design was originally part of a study with a parallel arm given combination APG-115 + Carboplatin. In the initial phase of that previous iteration, the combination arm was closed early for issues related to tolerability of the combination therapy. This study will continue as a single arm, monotherapy alone, Phase I/II study as approved by the UM Institutional Review Board as of June 2021.
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
- •Histologically documented malignant salivary gland cancers (including secretory glands of the aerodigestive tract) with or without metastases, not amenable to curative treatment; or there is documentation of patient refusal of curative treatment.
- •Previous mutational testing with no evidence of a p53 mutation
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- •Presence of measurable disease by CT scan per RECIST v1.1 with ≥ 20% increase in tumor burden in the preceding 12 months
- •Life expectancy of ≥12 weeks
- •Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- •Patients must be able to take oral medication without breaking/opening, crushing, dissolving, or chewing capsules
- •Adequate organ and marrow function obtained ≤ 2 weeks prior to enrollment
排除标准
- •Prior treatment with MDM2 inhibitors
- •Patients are not eligible if they have received any systemic anti-cancer therapy (including chemotherapy and/or hormone therapy) for salivary gland cancer within 4 weeks of the start of study therapy
- •Patients are not eligible if they have received any of the following within 4 weeks of the start of study therapy: live vaccines, antiretroviral drugs
- •Progressive disease within 6 months of the last dose of platinum-based chemotherapy
- •Patients with active brain metastases are excluded because of unknown penetration into the central nervous system (CNS). A confirmatory scan for asymptomatic patients is not required. Patients with a history of treated CNS metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 4 weeks between completion of radiotherapy and enrollment, and recovery from significant (Grade ≥ 3) acute toxicity.
- •A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
- •Patients (male and female) having procreative potential who are not willing or not able to use 2 adequate methods of contraception or practicing abstinence during the study and for 90 days following their last dose of treatment
- •Women who are pregnant or breast-feeding
研究组 & 干预措施
APG-115 monotherapy
APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.
干预措施: APG-115 (Drug)
APG-115 + Carboplatin [terminated]
APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. [Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.]
干预措施: Carboplatin (Drug)
APG-115 + Carboplatin [terminated]
APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. [Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.]
干预措施: APG-115 (Drug)
结局指标
主要结局
Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
时间窗: 42 days
DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
Maximally tolerated dose (MTD)
时间窗: 42 days
MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.
Overall response rate
时间窗: up to 12 months
Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR). Response will be assessed via RECIST v1.1.
次要结局
- Duration of response(Until death or end of study; up to approximately 5 years)
- Progression-free survival(Until death or end of study; up to approximately 5 years)
- Overall survival(Until death or end of study; up to approximately 5 years)
- Overall response rate by tumor histology(Until death or end of study; up to approximately 5 years)
- Disease control rate(Until death or end of study; up to approximately 5 years)