Fluzoparib + Bevacizumab vs Olaparib + Bevacizumab for Maintenance Therapy in HRD-Positive Advanced Ovarian Cancer
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.
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
- Female participants aged ≥ 18 years (age calculated on the date of signing the informed consent form).
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%.
- Disease staged as Stage III or Stage IV per the 2018 FIGO staging system.
- Confirmed HRD (Homologous Recombination Deficiency)-positive status via laboratory testing.
- 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.
- 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.
- ECOG Performance Status (ECOG-PS) score: 0 or 1.
- 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:
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.
- 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.
- Prior exposure to any PARP inhibitors, including but not limited to olaparib, niraparib, rucaparib, pamiparib and fluzoparib.
- Inability to swallow oral tablets normally, or presence of gastrointestinal dysfunction that may interfere with drug absorption, as judged by the investigator.
- History of intestinal obstruction or gastrointestinal perforation within the past 3 months.
- Symptomatic malignant ascites or pleural effusion requiring paracentesis or drainage; or history of ascites/pleural effusion drainage within 3 months prior to randomization.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: 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. |
|
Experimental: 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. |
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
12-month Progression-Free Survival (PFS) Rate
Time Frame: 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.
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression-Free Survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months
|
The time from randomization to the occurrence of disease progression (as per RECIST v1.1) or death from any cause, whichever occurs first.
|
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months
|
|
Overall Survival (OS)
Time Frame: From date of randomization until the date of death from any cause, assessed up to 96 months
|
The time from randomization to death due to any cause.
|
From date of randomization until the date of death from any cause, assessed up to 96 months
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urogenital Diseases
- Genital Diseases
- Endocrine System Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Genital Diseases, Female
- Endocrine Gland Neoplasms
- Ovarian Diseases
- Adnexal Diseases
- Genital Neoplasms, Female
- Gonadal Disorders
- Ovarian Neoplasms
Other Study ID Numbers
Other Study ID Numbers
- MA-OC-II-017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ovarian Cancer
-
NCT03297489CompletedFallopian Tube Carcinoma | Primary Peritoneal Carcinoma | Stage IIA Ovarian Cancer | Stage IIB Ovarian Cancer | Stage IIC Ovarian Cancer | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian Cancer | Stage IA Ovarian Cancer
-
NCT07311577RecruitingOvarian Cancer Metastatic | Ovarian Cancer Metastatic Recurrent
-
NCT07295132Not yet recruitingOvarian Cancer Recurrent | Platinum Sensitive Ovarian Cancer
-
NCT02082470CompletedCancer Survivor | Stage IIIA Ovarian Epithelial Cancer | Stage IIIB Ovarian Epithelial Cancer | Stage IIIC Ovarian Epithelial Cancer | Stage IIA Ovarian Epithelial Cancer | Stage IIB Ovarian Epithelial Cancer | Stage IIC Ovarian Epithelial Cancer | Stage IA Ovarian Epithelial Cancer | Stage IB Ovarian Epithelial Cancer | Stage IC Ovarian Epithelial Cancer
-
NCT04794322RecruitingOvarian Neoplasms | Fallopian Tube Neoplasms | Stage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage IVA Ovarian Cancer AJCC v8
-
NCT01080521CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous Cystadenocarcinoma
-
NCT06268665RecruitingBreast Cancer | Ovarian Cancer | Breast Neoplasm | Breast Carcinoma | Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage II | Invasive Breast Cancer | Cancer, Breast | Breast Cancer Stage III
-
NCT02981901UnknownOvarian Epithelial Cancer
-
NCT01275664TerminatedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Nausea and Vomiting | Ovarian Brenner Tumor | Ovarian Mucinous Cystadenocarcinoma | Undifferentiated Ovarian Carcinoma | Stage IIA Fallopian Tube Cancer | Stage IIA Ovarian Cancer
-
NCT01000259RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian Cancer
Clinical Trials on Fluzoparib+Bevacizumab
-
NCT05656131SuspendedAdvanced HER2 Negative Breast Carcinoma HRD+Breast Cancer
-
NCT07382713Not yet recruiting
-
NCT07353437Not yet recruiting
-
NCT05085626RecruitingAdvanced HER2 Negative Breast Carcinoma | HRD+Breast Cancer
-
NCT04521192CompletedHealthy Adult Subjects
-
NCT02575651CompletedAdvanced Solid Malignancies
-
NCT07321015Not yet recruitingTNBC, Triple Negative Breast Cancer | Platinum-sensitive | BRCA1/2 Mutation or Not
-
NCT05576389Enrolling by invitationGermline BRCA-mutated HER2-negative Breast Cancer
-
NCT04013048Completed