An Open-label, Global, Multi-Arm Study to Evaluate the Efficacy and Safety of Relacorilant in Combination With Different Treatment Regimens in Patients With Gynecological Cancers (BELLA)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 92
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase 2, open-label, global, multi-arm study to evaluate efficacy and safety of relacorilant in combination with other treatments in patients with gynecological cancers.
详细描述
This study is designed with the goal to add additional arms as new treatments become available. All arms will follow an independent and parallel design.
For Arms A and B, study treatment will comprise relacorilant combined with nab-paclitaxel, and bevacizumab and will begin on Cycle 1 Day 1 (C1D1). Each patient will receive relacorilant 150 mg administered orally under fed conditions, once daily for 3 consecutive days on the day before, the day of, and the day after nab-paclitaxel infusion (in Cycle 1 relacorilant is only given on 2 consecutive days, starting on C1D1), in combination with nab-paclitaxel (80 mg/m^2 intravenously [IV]) administered on Days 1, 8, and 15 of each 28-day cycle. Bevacizumab (10 mg/kg IV once every 2 weeks [Q2W]) will be administered on Days 1 and 15 of each 28-day cycle. Study treatment for Arm C will be similar to Arm A but does not include bevacizumab. Patients will receive treatment until they reach a protocol-defined event of progressive disease (PD), experience an unmanageable toxicity, or until other treatment discontinuation criteria are met.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Arms A and B
- •Histologic diagnosis of epithelial ovarian, primary peritoneal, or fallopian-tube carcinoma
- •Arm A Only: Platinum-resistant disease
- •Arm B Only: Platinum-sensitive disease who had progression while receiving treatment with a poly(ADP-ribose) polymerase (PARP) inhibitor
- •Life expectancy of ≥3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Able to swallow and retain oral medication
- •1 to 3 lines of prior systemic anticancer therapy
- •Adequate organ function
- •Negative pregnancy test for patients of childbearing potential
- •Stage III or IV, recurrent, or metastatic endometrial cancer
- •Life expectancy of ≥3 months
- •ECOG performance status of 0 or 1
- •Able to swallow and retain oral medication
- •Prior treatment with a platinum agent and an approved anti-Programmed Cell Death Ligand 1 (PD[L]1) antibody
- •1 to 2 lines of prior systemic anticancer therapy for endometrial cancer
- •Must consent to provide an available formalin-fixed paraffin-embedded (FFPE) tumor tissue block or recently cut sections
- •Adequate organ function
- •Negative pregnancy test for patients of childbearing potential
排除标准
- •Arm A and B
- •Arm A Only: Has progressed while receiving weekly paclitaxel or nab-paclitaxel
- •Prior enrollment in a clinical trial of relacorilant
- •Prior anticancer therapy related toxicities not resolved to grade ≤1
- •Any surgery within 4 weeks prior to enrollment
- •Wide-field radiation to more than 25% of marrow-bearing areas
- •Medical conditions requiring chronic or frequent treatment with corticosteroids
- •Concurrent treatment with mifepristone or other glucocorticoid receptor modulators
- •Peripheral neuropathy from any cause >Grade 1
- •Hypertension: ≥150 mm Hg systolic or ≥100 mm Hg diastolic
- •Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation
- •Bowel obstruction ≤12 weeks prior to study entry
- •Ascites or pleural effusions requiring therapeutic paracentesis
- •Untreated or symptomatic central nervous system metastases
- •History of other malignancy within 3 years prior to enrollment
- •Has received a live vaccine within 30 days prior to the study start date
- •Has progressed while receiving weekly paclitaxel or nab-paclitaxel
- •Prior enrollment in a clinical trial of relacorilant
- •Prior anticancer therapy related toxicities not resolved to grade ≤1
- •Any surgery within 4 weeks prior to enrollment
- •Wide-field radiation to more than 25% of marrow-bearing areas
- •Medical conditions requiring chronic or frequent treatment with corticosteroids
- •Concurrent treatment with mifepristone or other glucocorticoid receptor modulators
- •Peripheral neuropathy from any cause >Grade 1
- •Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation
- •Bowel obstruction ≤12 weeks prior to study entry
- •Ascites or pleural effusions requiring therapeutic paracentesis
- •History of other malignancy within 3 years prior to enrollment
- •Has received a live vaccine within 30 days prior to the study start date
- •Patients with central nervous system metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study.
研究组 & 干预措施
Arm A: Relacorilant in Combination with Nab-paclitaxel and Bevacizumab
In Arm A, patients with platinum-resistant ovarian cancer will receive the combination of relacorilant with nab-paclitaxel and bevacizumab.
干预措施: Relacorilant 150 mg once daily (QD) (Drug)
Arm B: Relacorilant in Combination with Nab-Paclitaxel and Bevacizumab
In Arm B, patients with platinum-sensitive ovarian cancer who have progressed while receiving treatment with a polymerase inhibitor will receive relacorilant in combination with nab-paclitaxel and bevacizumab.
干预措施: Nab-paclitaxel 80 mg/m^2 (Drug)
Arm A: Relacorilant in Combination with Nab-paclitaxel and Bevacizumab
In Arm A, patients with platinum-resistant ovarian cancer will receive the combination of relacorilant with nab-paclitaxel and bevacizumab.
干预措施: Nab-paclitaxel 80 mg/m^2 (Drug)
Arm B: Relacorilant in Combination with Nab-Paclitaxel and Bevacizumab
In Arm B, patients with platinum-sensitive ovarian cancer who have progressed while receiving treatment with a polymerase inhibitor will receive relacorilant in combination with nab-paclitaxel and bevacizumab.
干预措施: Relacorilant 150 mg once daily (QD) (Drug)
Arm C: Relacorilant in Combination with Nab-Paclitaxel
In Arm C, patients with previously-treated advanced, recurrent, or metastatic endometrial cancer will receive relacorilant in combination with nab-paclitaxel.
干预措施: Relacorilant 150 mg once daily (QD) (Drug)
Arm C: Relacorilant in Combination with Nab-Paclitaxel
In Arm C, patients with previously-treated advanced, recurrent, or metastatic endometrial cancer will receive relacorilant in combination with nab-paclitaxel.
干预措施: Nab-paclitaxel 80 mg/m^2 (Drug)
Arm A: Relacorilant in Combination with Nab-paclitaxel and Bevacizumab
In Arm A, patients with platinum-resistant ovarian cancer will receive the combination of relacorilant with nab-paclitaxel and bevacizumab.
干预措施: Bevacizumab 10 mg/kg (Drug)
Arm B: Relacorilant in Combination with Nab-Paclitaxel and Bevacizumab
In Arm B, patients with platinum-sensitive ovarian cancer who have progressed while receiving treatment with a polymerase inhibitor will receive relacorilant in combination with nab-paclitaxel and bevacizumab.
干预措施: Bevacizumab 10 mg/kg (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Date of first dose until PD or death, up to 18 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 occurs first.
次要结局
- Objective Response Rate (ORR)(Date of first dose until PD or death, up to 18 months)
- Duration of Response (DOR)(Time of first objective response until PD or death, up to 18 months)
- Clinical Benefit Rate (CBR)(Week 24)
- Overall Survival (OS)(Date of first dose up to 6, 12, and 18 months)
- Number of patients with one or more adverse events(Date of first dose up to 30 days after last dose)
- Area under the plasma concentration-time curve (AUC) of relacorilant(On Cycle 1 Day 8 (each cycle is 28 days))
- Maximum plasma concentration (Cmax) of relacorilant(On Cycle1 Day 8 (each cycle is 28 days))
- Trough plasma concentrations (Cmin) of relacorilant(On Cycle 2 Day 8 through the last cycle (up to 12 cycles, each cycle is 28 days))
- Objective Response Rate (ORR)(Date of first dose until PD or death, up to 18 months)
- Best Overall Response Rate (BOR)(Date of first dose until PD or death, up to 18 months)
- Clinical Benefit Rate (CBR)(Week 24)
- Overall Survival (OS)(Date of first dose up to 6, 12, and 18 months)
- Number of patients with one or more adverse events(Date of first dose up to 30 days after last dose)
- Duration of Response (DOR)(Time of first objective response until PD or death, up to 18 months)