A Phase 1/2a/3 Evaluation of the Safety and Efficacy of Adding AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 294
- 试验地点
- 41
- 主要终点
- Measure the Progression Free Survival (PFS)- Part 3 ( Phase 3)
研究概览
简要总结
This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to standard platinum-based chemotherapy concurrently in Subjects with Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma.
详细描述
This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818(Anlotinib, INN: Catequentinib) to standard platinum-based chemotherapy concurrently and continued as a maintenance therapy for up to 12 months, in subjects with recurrent or metastatic endometrial, ovarian, fallopian, primary peritoneal, or cervical carcinoma. AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions.
Phase 1 & 2: This study is divided into two parts. The objective of Part 1 is the evaluation of the safety and tolerability of adding oral AL3818 to standard carboplatin plus paclitaxel chemotherapy for a cycle of 21 days to determine the recommended Phase II dose (RP2D). Phase 1 / Part 1 is now complete. Part 2-The objective of Part 2 is evaluation of preliminary efficacy and the safety of adding oral AL3818 at the RP2D determined in Part 1 to carboplatin and paclitaxel chemotherapy for 6 cycles. Continuous maintenance mono therapy with 14 days on and 7 days off regimen at the RP2D will be conducted up to 12 months and is extendable beyond until disease progression. Phase I is closed and Phase 2 is closed.
Phase 3: This study is currently a Phase III, multi-center, randomized trial with active control designed to evaluate the efficacy and safety of AL3818 8 mg plus background treatment (Active Arm) vs background treatment alone (Control Arm), where three background treatments, weekly paclitaxel, pegylated liposomal doxorubicin (PLD), and topotecan are utilized. Oral AL3818 8 mg may be given concurrently with background treatment or alone if the background treatment must be discontinued due to its toxicity for up to 24 cycles of therapy, in subjects with recurrent or metastatic platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 is open.
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
- Female
- 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
Phase 3 -Active Treatment Arm
Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: AL3818 (Drug)
Phase 3 -Active Treatment Arm
Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Paclitaxel (Drug)
Phase 3 -Active Treatment Arm
Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Pegylated Liposomal Doxorubicin (PLD) (Drug)
Phase 3 -Active Treatment Arm
Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Topotecan (Drug)
Phase 3-Control Treatment Arm
Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Paclitaxel (Drug)
Phase 3-Control Treatment Arm
Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Pegylated Liposomal Doxorubicin (PLD) (Drug)
Phase 3-Control Treatment Arm
Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:
- Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
- Pegylated liposomal doxorubicin (PLD)
- Topotecan
干预措施: Topotecan (Drug)
Phase 1b: AL3818 plus carboplatin and paclitaxel
Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.
干预措施: Carboplatin (Drug)
Phase 1b: AL3818 plus carboplatin and paclitaxel
Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.
干预措施: Paclitaxel (Drug)
Phase 1b: AL3818 plus carboplatin and paclitaxel
Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.
干预措施: AL3818 (Drug)
Phase 2a: AL3818 plus carboplatin and paclitaxel
Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.
干预措施: Carboplatin (Drug)
Phase 2a: AL3818 plus carboplatin and paclitaxel
Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.
干预措施: Paclitaxel (Drug)
Phase 2a: AL3818 plus carboplatin and paclitaxel
Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.
干预措施: AL3818 (Drug)
结局指标
主要结局
Measure the Progression Free Survival (PFS)- Part 3 ( Phase 3)
时间窗: 12 Months
To evaluate the efficacy between the Active Arm (AL3818 in combination with background chemotherapy) and Control Arm (background chemotherapy alone arm) as measured by the primary endpoint of Progression Free Survival (PFS).
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
时间窗: Cycle 1 (21-days)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Objective Response Rates (ORR) - Part 2 (Phase 2a)
时间窗: 12 months
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. ORR is measured by the number of complete (CR) and partial responses (PR)
次要结局
- Number of Participants with Adverse Events as a measure of safety and toxicity of 21-Day cycles of AL3818 as measured by incidence and severity of treatment-related adverse events (TRAE) - Part 1 (Phase 1b)(Cycle 1 (Day 21))
- Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)(12 Months)
- Duration Of Response - Part 3 ( Phase 3)(12 Months)
- Overall Survival - Part 3 ( Phase 3)(12 Months)
- Objective Response Rate- Part 3 ( Phase 3)(12 Months)
- Progression-Free Survival (PFS) - Part 2 (Phase 2a)(Duration of time from the start of treatment to the time of documented disease progression or death, whichever comes first, followed for 12 months.)
- Overall Survival (OS) - Part 2 (Phase 2a)(Cycle 1 Day 1 up to 5 years)