A Randomized, Controlled, Open-Label, Phase 2 Trial of SGI-110 and Carboplatin in Subjects With Platinum-Resistant Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 24
- 主要终点
- Stage 1: Dose Limiting Toxicities
研究概览
简要总结
A 2-part, Phase 2 controlled, open-label, randomized study in participants with platinum-resistant recurrent ovarian cancer. In Part 1, participants received SGI-110 and carboplatin. The optimum dose of SGI-110 (guadecitabine) was identified in Part 1 based on safety and efficacy. In Part 2, participants were randomized to receive the dose identified in Part 1 plus carboplatin or one of four treatment of choice at the discretion of the investigator. The treatment of choice consisted of topotecan, pegylated liposomal doxorubicin, paclitaxel or gemcitabine.
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
- •Participants who are women 18 years of age or older.
- •Participants who have histologically or cytologically confirmed recurrent high-grade serous epithelial ovarian cancer (Grade 2 or 3), primary peritoneal carcinomatosis or fallopian tube cancer.
- •Participants who have platinum-resistant disease (defined as having relapsed within 6 months of her last platinum-containing regimen). There is no limit on the number of prior treatment regimens in Part
- •In Part 2, participants may have had no more than 3 prior cytotoxic treatment regimens, excluding adjuvant or maintenance therapy.
- •Participants must have had prior paclitaxel treatment.
- •Participants who have measurable disease according to RECIST v1.1 or detectable disease.
- •Participants with ECOG performance status of 0 or
- •Participants with acceptable organ function.
- •Participants must be at least 3 weeks from last chemotherapy.
排除标准
- •Participants who have hypersensitivity to SGI-110 and/or carboplatin or other components of these drug products.
- •Participants who have received prior therapy with any hypomethylating agents.
- •Participants who are refractory to platinum treatment i.e., progressed while on platinum treatment.
- •Participants with abnormal left ventricular ejection fraction.
- •Participants with Grade 2 or greater neuropathy.
- •Participants with known brain metastases.
- •Participants with known history of HIV, HCV or HBV.
研究组 & 干预措施
SGI-110 + Carboplatin
Stage 1 was a safety lead-in stage with a dose escalation design. Participants were evaluated with the combination of SGI-110 (guadecitabine) plus carboplatin (G+C), given as 28-day treatment cycles: guadecitabine administered subcutaneous (SC) daily on Days 1-5, at a starting dose of 45 mg/m2/day in Cohort 1, followed by carboplatin intravenous (IV) based on a targeted dose of area under the curve (AUC) 5 on Day 8. After dose limiting toxicities were noted, guadecitabine dose was reduced to 30 mg/m2/day for subsequent cycles for 4 participants. Cohort 2 received 30 mg/m2/day guadecitabine and carboplatin IV AUC 4.
干预措施: SGI-110 (Drug)
SGI-110 + Carboplatin
Stage 1 was a safety lead-in stage with a dose escalation design. Participants were evaluated with the combination of SGI-110 (guadecitabine) plus carboplatin (G+C), given as 28-day treatment cycles: guadecitabine administered subcutaneous (SC) daily on Days 1-5, at a starting dose of 45 mg/m2/day in Cohort 1, followed by carboplatin intravenous (IV) based on a targeted dose of area under the curve (AUC) 5 on Day 8. After dose limiting toxicities were noted, guadecitabine dose was reduced to 30 mg/m2/day for subsequent cycles for 4 participants. Cohort 2 received 30 mg/m2/day guadecitabine and carboplatin IV AUC 4.
干预措施: Carboplatin (Drug)
SGI-110 + Carboplatin or TC
Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
干预措施: SGI-110 (Drug)
SGI-110 + Carboplatin or TC
Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
干预措施: Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) (Drug)
SGI-110 + Carboplatin or TC
Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Stage 1: Dose Limiting Toxicities
时间窗: Up to 12 months
Number of participants with dose limiting toxicities (DLTs) in Stage 1
Stage 2: Progression Free Survival
时间窗: Up to 24 months
Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment \[guadecitabine+carboplatin (G+C) or treatment choice (TC)\] until disease progression or unacceptable treatment-related toxicity occurred.
次要结局
- Objective Response Rate(Up to 24 months)
- Progression Free Survival at 6 Months(6 months)
- Clinical Benefit Rate(Up to 24 months)
- CA-125 Levels(Up to 24 months)
- Duration of Response(Up to 24 months)
- Overall Survival(Up to 24 months)
- Stage 1: Pharmacokinetic Parameter Cmax(Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles))
- Stage 1: Pharmacokinetic Parameter Tmax(Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles))
- Stage 1: Pharmacokinetic Parameter AUC0-8(Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles))