A Phase 2, Single-Arm Trial of Relacorilant in Combination With Nab-Paclitaxel and Gemcitabine in Chemotherapy-Naïve Patients With Metastatic Pancreatic Adenocarcinoma (TRIDENT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 16
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a 2-part, Phase 2 study to evaluate the safety, tolerability, dosing, pharmacokinetics (PK), and efficacy of relacorilant in combination with nab-paclitaxel and gemcitabine in chemotherapy-naïve patients with metastatic pancreatic adenocarcinoma (PDAC).
详细描述
This study will include 2 parts. In Part 1 (dose finding), approximately 6 patients will be enrolled to individual dose-finding cohorts. Cohorts will receive various dose concentrations of relacorilant, nab-paclitaxel, and gemcitabine at various dosing schedules. In all dose-finding cohorts, relacorilant will be administered orally under fed conditions, once daily for 3 days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine. Enrollment will be paused after each cohort has been filled until the safety review committee (SRC) provides recommendations. If maximum tolerated dose (MTD) criteria are not met in a cohort, then either a dose-finding cohort at a more intense dose and/or schedule may be enrolled, or a dose and schedule at/below the MTD may be selected as the optimal dose and schedule, and Part 2 may be initiated. If MTD criteria are met, then a dose-finding cohort at a less intense dose and/or schedule may be enrolled, or dose-finding may end without proceeding to Part 2.
In Part 2 (expansion), each patient will receive the optimal dose and schedule of relacorilant, nab-paclitaxel, and gemcitabine as identified in Part 1. Analysis of Part 2 will include data for patients from Part 1 who were enrolled in the optimal dose and schedule used in Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Signed and dated informed consent form prior to screening procedures
- •Histologic diagnosis or cytologic diagnosis of pancreatic adenocarcinoma (PDAC)
- •Initial diagnosis of metastatic disease occurred ≤9 weeks prior to enrollment in the study
- •Life expectancy of ≥3 months
- •Radiographic confirmation of metastatic disease with at least 1 distant tumor metastasis measurable on radiology imaging per RECIST version 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Able to provide informed consent and comply with protocol requirements
- •Able to swallow and retain oral medication and does not have uncontrolled emesis
- •Has adequate gastrointestinal absorption
- •Received no prior systemic anticancer chemotherapy to treat metastatic PDAC. Treatment of PDAC with a single agent RAS inhibitor is permitted.
- •If a patient received prior treatment of PDAC with chemotherapy, disease progression must have occurred >12 months after completing the last dose, and no persistent treatment-related toxicities can be present.
- •Adequate organ function
- •Negative pregnancy test for patients of childbearing potential
- •Agree to use protocol defined precautions to avoid pregnancy
排除标准
- •Any major surgery within 4 weeks prior to enrollment
- •Prior treatment as follows:
- •Radiotherapy, surgery, chemotherapy, immunotherapy, investigational therapy for the treatment of metastatic disease
- •Systemic, inhaled, or prescription strength topical corticosteroids within 5 times the half-life of the corticosteroid used prior to first dose of study drug
- •Received gemcitabine or nab-paclitaxel to treat their PDAC
- •Known germline or somatic breast cancer gene (BRCA) mutation
- •Peripheral neuropathy from any cause >Grade 1
- •Medical conditions requiring chronic or frequent treatment with corticosteroids
- •History of severe hypersensitivity or severe reaction to any of study drugs or their excipients
- •Concurrent treatment with mifepristone or other glucocorticoid receptor modulators.
- •Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation
- •Active infection with HIV, hepatitis C or hepatitis B virus
- •Known untreated parenchymal brain metastasis or uncontrolled central nervous system metastases
- •History of other malignancy within 3 years prior to enrollment
- •Taking protocol-prohibited medications
- •Concurrent treatment with other investigational treatment studies for cancer
- •Has received a live vaccine within 30 days prior to the study start date
研究组 & 干预措施
Relacorilant in Combination with Nab-paclitaxel and Gemcitabine
The patient will receive relacorilant administered orally under fed conditions, once daily for 3 consecutive days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine intravenous (IV) infusions. Various dose levels and dosing schedules of relacorilant, nab-paclitaxel, and gemcitabine will be evaluated. On days when relacorilant, nab-paclitaxel, and gemcitabine are administered, relacorilant will be administered first, then nab-paclitaxel, and gemcitabine last.
干预措施: Relacorilant (Drug)
Relacorilant in Combination with Nab-paclitaxel and Gemcitabine
The patient will receive relacorilant administered orally under fed conditions, once daily for 3 consecutive days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine intravenous (IV) infusions. Various dose levels and dosing schedules of relacorilant, nab-paclitaxel, and gemcitabine will be evaluated. On days when relacorilant, nab-paclitaxel, and gemcitabine are administered, relacorilant will be administered first, then nab-paclitaxel, and gemcitabine last.
干预措施: Gemcitabine (Drug)
Relacorilant in Combination with Nab-paclitaxel and Gemcitabine
The patient will receive relacorilant administered orally under fed conditions, once daily for 3 consecutive days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine intravenous (IV) infusions. Various dose levels and dosing schedules of relacorilant, nab-paclitaxel, and gemcitabine will be evaluated. On days when relacorilant, nab-paclitaxel, and gemcitabine are administered, relacorilant will be administered first, then nab-paclitaxel, and gemcitabine last.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
To evaluate PFS as the time from enrollment until first documented progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by the Investigator, or death due to any cause, whichever comes first.
次要结局
- Objective Response Rate (ORR)(From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months)
- Overall Survival (OS)(From date of enrollment until the date of death from any cause, whichever comes first, assessed up to 19 months)
- Best Overall Response (BOR)(From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months)
- Duration of Response (DoR)(From date of first objective response until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months)
- Clinical Benefit Rate (CBR)(Week 24)
- Number of Patients with 1 or More Adverse Events(Time of first dose up to 30 days after last dose)
- Maximum Plasma Concentration (Cmax) of Relacorilant(Pre- and postdose on Cycle 1 Day 8 (each cycle is 28 days))
- Area Under the Plasma Concentration-time Curve (AUC) of Relacorilant(Pre- and postdose on Cycle 1 Day 8 (each cycle is 28 days))
- Cmax of Nab-paclitaxel(Postdose on Cycle 1 Day 8 (each cycle is 28 days))
- AUC of Nab-paclitaxel(Postdose on Cycle 1 Day 8 (each cycle is 28 days))
- Cancer Antigen 19-9 (CA19-9) Kinetics(Baseline to Weeks 4, 8, and 16)