Pamiparib in Combination With Surufatinib in Patients With Platinum-resistant Ovarian Cancer Who Received Prior Poly (ADP-ribose) Polymerase (PARP) Inhibitors: a Multicenter, Single-arm, Phase Ib/II Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 dose (RP2D) (Phase Ib)
研究概览
简要总结
A number of studies suggest that the combination of PARP inhibitors and antiangiogenic agents produce synergistic activities. Pamiparib is a small molecule inhibitor selectivity for both PARP1 and PARP2. Surufatinib is a novel small-molecule inhibitor that simultaneously targets tumor angiogenesis (via Vascular Endothelial Growth Factor Receptor [VEGFR]1, VEGFR 2, VEGFR3 and Fibroblast Growth Factor Receptor 1 [FGFR1]) and immune evasion (via Colony Stimulating Factor 1 Receptor [CSF1R]). In this trial, we aimed to evaluate the efficacy, safety and tolerability of pamiparib in combination with surufatinib in patients with platinum-resistant ovarian cancer who received prior PARP inhibitors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form;
- •Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer;
- •Platinum-resistant disease, defined as progression within 6 months from completion of most recent platinum-containing therapy. Subject may have been treated with additional regimen(s) subsequent to determination of platinum resistance;
- •Patients must have received one prior PARP inhibitor therapy, and there must be a ≥ 6 month interval since treatment;
- •Female participants age 18-75 years;
- •Has measurable lesion per RECIST v1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Life expectancy ≥ 3 months;
- •Patients must have normal organ and bone marrow function;
- •Women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices [IUDs]) throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s).
排除标准
- •Histological diagnosis of mucinous adenocarcinoma;
- •Has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs);
- •Known or suspected allergy to any of study drugs;
- •Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York heart association [NYHA] class > 2, unstable angina, myocardial infarction, cardiac arrhythmia associated with hemodynamic instability (including corrected QT (QTc) interval ≥ 450 ms in men, ≥ 470 ms in female);
- •Has active ulcers, gastrointestinal perforation or obstruction;
- •Active bleeding or pathologic condition that carries a high risk of bleeding;
- •Inadequately controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg) with or without treatment;
- •Major surgery within 28 days of starting study treatment;
- •Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g;
- •Uncontrolled pericardial or pleural or peritoneal effusions;
- •Has a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include in situ cervical cancer, non-melanoma skin cancer, or superficial bladder tumors that has undergone potentially curative therapy;
- •Known Human Immunodeficiency Virus (HIV) infection;
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
- •Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study.
研究组 & 干预措施
Pamiparib + Surufatinib (Phase Ib/II)
Phase Ib:
A dose de-escalation schedule is used in the phase Ib dose finding part. Dose Level 1 (starting dose): pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 250 mg administered orally once daily on a 21-day treatment cycle. If ≥2/6 patients experience a dose limiting toxicity (DLT), we will de-escalate to Dose Level 2: pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 200 mg administered orally once daily on a 21-day treatment cycle. Approximately 3-12 patients will be enrolled in phase Ib study.
Phase II:
The phase II part will begin once the recommended phase 2 dose (RP2D) of surufatinib have been determined in the Phase Ib in order to assess antitumor activity of pamiparib and surufatinib combination. In phase II study, pamiparib 40 mg orally twice daily and surufatinib PR2D will be administered.
干预措施: Pamiparib (Drug)
Pamiparib + Surufatinib (Phase Ib/II)
Phase Ib:
A dose de-escalation schedule is used in the phase Ib dose finding part. Dose Level 1 (starting dose): pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 250 mg administered orally once daily on a 21-day treatment cycle. If ≥2/6 patients experience a dose limiting toxicity (DLT), we will de-escalate to Dose Level 2: pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 200 mg administered orally once daily on a 21-day treatment cycle. Approximately 3-12 patients will be enrolled in phase Ib study.
Phase II:
The phase II part will begin once the recommended phase 2 dose (RP2D) of surufatinib have been determined in the Phase Ib in order to assess antitumor activity of pamiparib and surufatinib combination. In phase II study, pamiparib 40 mg orally twice daily and surufatinib PR2D will be administered.
干预措施: Surufatinib (Drug)
结局指标
主要结局
Recommended Phase 2 dose (RP2D) (Phase Ib)
时间窗: first 21 days of treatment
Determine the RP2D of the pamiparib and surufatinib combination
The 6-month progression-free survival (PFS) rate (Phase II)
时间窗: from the first drug administration up to two years
The percentage of patients alive without documented progression 6 months after treatment initiation.
次要结局
- Duration of response (DOR)(from the first drug administration up to two years)
- Overall survival (OS)(from the first drug administration up to 2 years)
- Disease Control Rate (DCR)(from the first drug administration up to two years)
- Safety and tolerability(up to 90 days after last study treatment administration)
- Patient Reported Outcomes (PROs)(from the first drug administration up to two years)
- Objective response rate (ORR)(from the first drug administration up to two years)
研究者
Xin Huang
Prof.
Sun Yat-sen University