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Fluzoparib + Bevacizumab vs Olaparib + Bevacizumab for Maintenance Therapy in HRD-Positive Advanced Ovarian Cancer

2026年6月10日 更新者:Beihua Kong、Shandong University

A Multicenter, Randomized, Open-Label Exploratory Study of Fluzoparib Plus Bevacizumab Versus Olaparib Plus Bevacizumab for Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With HRD-Positive Advanced Ovarian Cancer

The PAOLA-1 trial demonstrated that for HRD-positive patients who received first-line chemotherapy combined with bevacizumab, sequential maintenance therapy with olaparib plus bevacizumab yielded a progression-free survival (PFS) of up to 46.8 months, with an olaparib-related treatment discontinuation rate of approximately 20%.

The combination of olaparib and bevacizumab has been recommended by multiple clinical guidelines as the first-line maintenance regimen for HRD-positive patients treated with first-line chemotherapy plus bevacizumab. This regimen has obtained approved indications and been covered by national medical insurance. In clinical practice, around 30% of patients receiving chemotherapy plus bevacizumab adopt olaparib combined with bevacizumab for first-line maintenance treatment.

Fluzoparib has been approved in China for first-line maintenance therapy in the overall patient population. The treatment discontinuation rate of fluzoparib plus apatinib is merely about 2%. However, there is currently no available data regarding fluzoparib combined with bevacizumab in the HRD-positive population, and the clinical value of this regimen remains to be further explored.

This study aims to generate efficacy and safety data for olaparib plus bevacizumab versus fluzoparib plus bevacizumab in HRD-positive patients who have undergone first-line chemotherapy combined with bevacizumab, so as to provide objective evidence for clinical medication decisions.

研究概览

研究类型

介入性

注册 (估计的)

120

阶段

  • 阶段2

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. The participant voluntarily agrees to take part in the study, signs the informed consent form, demonstrates good treatment compliance, and is willing to complete scheduled follow-up.
  2. Female participants aged ≥ 18 years (age calculated on the date of signing the informed consent form).
  3. Newly pathologically diagnosed high-grade (or moderately/poorly differentiated) serous ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma; or grade II and higher ovarian endometrioid adenocarcinoma.

    For mixed tumors: The proportion of high-grade serous component or grade II+ endometrioid component must exceed 50%.

  4. Disease staged as Stage III or Stage IV per the 2018 FIGO staging system.
  5. Confirmed HRD (Homologous Recombination Deficiency)-positive status via laboratory testing.
  6. The participant has received 6 to 9 cycles of platinum-based chemotherapy. For participants who cannot tolerate chemotherapy for documented reasons, a minimum of 4 cycles of platinum-based chemotherapy is required.Prior to randomization, participants must have received bevacizumab combined with platinum-based chemotherapy for at least the final 3 cycles, with a minimum of 3 cycles of bevacizumab administration.For participants undergoing interval debulking surgery (IDS), a minimum of 2 cycles of bevacizumab combined with the final 3 cycles of platinum-based chemotherapy is acceptable.
  7. Prior to randomization, participants must have No Evidence of Disease (NED), or be assessed as having achieved Complete Response (CR) or Partial Response (PR) after first-line platinum-based chemotherapy, and maintain this status until initiation of study treatment. Randomization and study drug administration must be completed within 8 weeks after the last dose of chemotherapy.
  8. ECOG Performance Status (ECOG-PS) score: 0 or 1.
  9. Major organ function meets the following requirements. Use of any blood products or hematopoietic growth factors is prohibited within 14 days prior to randomization:

Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 90 × 10⁹/L Hemoglobin ≥ 9 g/dL Serum albumin ≥ 3 g/dL Total bilirubin ≤ 1.5 × ULN Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN 10、For women of childbearing potential: A negative serum pregnancy test result must be obtained within 72 hours prior to randomization. Participants must agree to use one medically approved contraceptive method throughout the study treatment period and for 6 months after the last dose of study drug. Participants must not be breastfeeding.

Exclusion Criteria:

  1. History of other untreated malignant tumors within the past 5 years, or concurrent untreated malignant tumors.

    Exceptions: cured thyroid carcinoma, cutaneous basal cell carcinoma, cervical carcinoma in situ, and breast cancer with no recurrence for more than 3 years after radical resection.

  2. Presence of untreated central nervous system (CNS) metastases. Exception: Participants who have received definitive systemic or radical treatment (radiotherapy or surgery) for brain or meningeal metastases, with radiologically confirmed stable disease for at least 1 month, who have discontinued systemic glucocorticoid therapy (prednisone > 10 mg/day or equivalent glucocorticoids) for more than 2 weeks and have no associated clinical symptoms are eligible.
  3. Prior exposure to any PARP inhibitors, including but not limited to olaparib, niraparib, rucaparib, pamiparib and fluzoparib.
  4. Inability to swallow oral tablets normally, or presence of gastrointestinal dysfunction that may interfere with drug absorption, as judged by the investigator.
  5. History of intestinal obstruction or gastrointestinal perforation within the past 3 months.
  6. Symptomatic malignant ascites or pleural effusion requiring paracentesis or drainage; or history of ascites/pleural effusion drainage within 3 months prior to randomization.
  7. Uncontrolled cardiac symptoms or diseases, including:

(1) Heart failure with NYHA Functional Class ≥ 2; (2) Unstable angina pectoris; (3) Myocardial infarction within the past 1 year; (4) Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) QTc interval > 470 ms. 8、Coagulopathy defined as International Normalized Ratio (INR) > 1.5 or Prothrombin Time (PT) > ULN + 4 seconds; presence of bleeding diathesis, or receipt of thrombolytic or systemic anticoagulant therapy.

Exception: Prophylactic anticoagulation with low-dose low-molecular-weight heparin or oral aspirin is allowed during the study.

9、Clinically significant bleeding events or definite bleeding diathesis within 3 months prior to randomization (e.g., gastrointestinal hemorrhage, hemorrhagic gastric ulcer, vasculitis).

10、If the baseline fecal occult blood test is positive, repeat testing is permitted. If the repeat test remains positive, clinical evaluation is required, and gastroscopy shall be performed if necessary.

11、Presence of active ulcers, unhealed wounds or fractures. Uncontrolled hypertension despite standard antihypertensive therapy (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).

12、Any bleeding event graded ≥ Grade 2 per CTCAE v6.0 within 4 weeks prior to randomization.

13、Active infection, or unexplained fever > 38.5 °C during the screening period or prior to randomization.

14、Congenital or acquired immunodeficiency (e.g., HIV infection), or active viral hepatitis.

15、Prior radiotherapy, chemotherapy, hormonal therapy or molecular targeted therapy completed less than 4 weeks before study drug administration (less than 5 drug half-lives for oral molecular targeted agents). Adverse events from previous anti-tumor therapies have not recovered to Grade ≤ 1 per CTCAE v6.0 (alopecia is excluded).

16、History of arterial or venous thromboembolic events within 6 months prior to randomization, including cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism, etc.

17、Hereditary or acquired bleeding disorders or coagulation dysfunction (e.g., hemophilia, thrombocytopenia).

18、Plan to receive other systemic anti-tumor therapy during the study period. 19、Any other medical conditions or circumstances that may lead to premature termination of the study, as judged by the investigator.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:fluzoparib + bevacizumab

Fluzoparib Capsules: Administered orally at a dose of 3 capsules (150 mg) twice daily for a total duration of 2 consecutive years. Morning and evening dosing is allowed, and the drug may be taken with or without food; it is recommended to take each dose within 0.5 hours after breakfast and dinner, with continuous administration throughout the treatment period.

Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months.

Fluzoparib Capsules: Administered orally at a dose of 3 capsules (150 mg) twice daily for a total duration of 2 consecutive years. Morning and evening dosing is allowed, and the drug may be taken with or without food; it is recommended to take each dose within 0.5 hours after breakfast and dinner, with continuous administration throughout the treatment period.

Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months.

实验性的:olaparib plus bevacizumab

Administered orally at a dose of 2 tablets (300 mg) twice daily for a total duration of 2 consecutive years. It is recommended to take the drug at fixed times in the morning and evening on an empty stomach (either 1 hour before a meal or 2 hours after a meal), with continuous administration throughout the treatment period.

Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months.

Olaparib Tablets: Administered orally at a dose of 2 tablets (300 mg) twice daily for a total duration of 2 consecutive years. It is recommended to take the drug at fixed times in the morning and evening on an empty stomach (either 1 hour before a meal or 2 hours after a meal), with continuous administration throughout the treatment period.

Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
12-month Progression-Free Survival (PFS) Rate
大体时间:From date of randomization up to 12 months post-randomization for rate assessment; overall study assessment is conducted up to 96 months.
The proportion of participants who remain free of disease progression (as per RECIST v1.1) or death from any cause at 12 months after randomization.
From date of randomization up to 12 months post-randomization for rate assessment; overall study assessment is conducted up to 96 months.

次要结果测量

结果测量
措施说明
大体时间
无进展生存(PFS)
大体时间:从随机分组的日期到首先记录的进展或死亡日期的任何原因(以第一个为准)评估长达96个月
从随机化到发生疾病进展的时间(根据recist v1.1)或任何原因的死亡,无论是先发生的。
从随机分组的日期到首先记录的进展或死亡日期的任何原因(以第一个为准)评估长达96个月
总生存(OS)
大体时间:从随机日期到任何原因的死亡日期,最多可评估96个月
由于任何原因而导致的随机分组到死亡的时间。
从随机日期到任何原因的死亡日期,最多可评估96个月

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年6月30日

初级完成 (估计的)

2031年2月28日

研究完成 (估计的)

2031年2月28日

研究注册日期

首次提交

2026年6月10日

首先提交符合 QC 标准的

2026年6月10日

首次发布 (实际的)

2026年6月15日

研究记录更新

最后更新发布 (实际的)

2026年6月15日

上次提交的符合 QC 标准的更新

2026年6月10日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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