Fluzoparib with or without Bevacizumab for treating advanced ovarian cancer

A Randomized, Open-Label, Multi-Cohort Study of Fluzoparib Monotherapy or in Combination With Bevacizumab as Neoadjuvant Therapy in Patients With Advanced Ovarian Cancer

This study is testing whether a new drug called Fluzoparib, alone or with another drug called Bevacizumab, can help people with advanced ovarian cancer caused by BRCA1/2 mutations do better than standard chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 105 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Qilu Hospital of Shandong University (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, prednisone
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT06735326 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of Fluzoparib alone and in combination with Bevacizumab, compared to standard chemotherapy, as neoadjuvant treatments for patients with newly diagnosed, germline BRCA1/2-mutated advanced ovarian cancer. The study is randomized and open-label, involving multiple centers and cohorts. It aims to assess the objective response rate, R0 resection rate, overall survival, and progression-free survival, while also evaluating safety and patient-reported outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed, FIGO stage III-IV high-grade serous ovarian cancer or related conditions who are unable to achieve R0 resection or tolerate surgery.

Not a fit: Patients with early-stage ovarian cancer or those who can tolerate surgery and achieve R0 resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could improve outcomes for patients with advanced ovarian cancer by providing more effective neoadjuvant therapy options.

How similar studies have performed: Other studies have shown promising results with similar approaches in treating advanced ovarian cancer, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. The subject voluntarily agrees to participate and signs the informed consent form.
2. Age ≥18 years (calculated as of the date of signing the informed consent).
3. Pathologically diagnosed with newly diagnosed, FIGO stage III-IV high-grade (or moderate/low-grade) serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; grade ≥II endometrioid adenocarcinoma of the ovary; Mixed tumors: high-grade serous or ≥II grade endometrioid component must be \>50%.
4. The subject has at least one measurable lesion that can be assessed by CT or MRI (RECIST v1.1).
5. According to the investigator's assessment, the patient is unable to achieve R0 resection or cannot tolerate surgery.

   a) Criteria for determining inability to achieve R0 resection include: i. Fagotti laparoscopic score ≥8. ii. If laparoscopic assessment is difficult, an upper abdominal Suidan's CT score ≥3.

   b) Criteria for inability to tolerate surgery include: i. Body mass index (BMI) ≥40. ii. Multiple chronic diseases. iii. Malnutrition or hypoalbuminemia. iv. Moderate to large ascites. v. Newly diagnosed venous thromboembolism. vi. ECOG performance status \>2. vii. Other reasons judged by the investigator.
6. Expected survival \>12 weeks.
7. ECOG performance status: 0-2.
8. Confirmed germline BRCA1/2 mutations by professional genetic testing.
9. Function of major organs meets the following requirements (no blood products or colony-stimulating factors allowed within 14 days prior to the first dose):

   1. Absolute neutrophil count ≥1.5 × 10\^9/L.
   2. Platelet count ≥100 × 10\^9/L.
   3. Hemoglobin ≥9 g/dL.
   4. Serum albumin ≥3 g/dL.
   5. Bilirubin ≤1.5 times the upper limit of normal (ULN).
   6. ALT and AST ≤2.5 times ULN, must be ≤5 times ULN in the presence of liver metastases.
   7. Serum creatinine ≤1.5 times ULN, or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula).
10. Female patients of childbearing potential must have a negative blood pregnancy test within one week before the first dose and are not breastfeeding. They must agree to use effective contraception during the study and for 6 months after the last dose of Bevacizumab/Fluzoparib/chemotherapy. Pregnancy, if confirmed, must be terminated as soon as possible.
11. The subject is willing to cooperate in completing quality of life surveys during the treatment and follow-up periods and agrees to have the survey results used for clinical research.

Exclusion Criteria:

1. Patients with other untreated malignant tumors within the past 5 years, except for cured skin basal cell carcinoma, cervical carcinoma in situ, and breast cancer without relapse for over 3 years after radical surgery.
2. Patients with untreated central nervous system metastases. Patients who have previously received systemic or curative brain or meningeal metastasis treatment (radiotherapy or surgery) and have stable imaging confirmed for at least 1 month, and have stopped systemic steroid treatment (dosage \>10 mg/day prednisone or equivalent) for more than 2 weeks, and have no clinical symptoms, may be included.
3. Patients who have previously received treatment with known or potential PARP inhibitors or Bevacizumab.
4. Patients unable to swallow tablets or with gastrointestinal dysfunction that may affect drug absorption, as judged by the investigator.
5. Patients who have experienced bowel obstruction or gastrointestinal perforation within the last 3 months.
6. Patients with poorly controlled heart conditions or diseases, such as:

   1. NYHA Class II or higher heart failure.
   2. Unstable angina.
   3. Myocardial infarction within 1 year.
   4. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
   5. QTc \>470 ms.
7. Patients with clinically significant bleeding symptoms or a clear bleeding tendency (such as gastrointestinal bleeding, bleeding ulcers, or vasculitis) within 3 months prior to the first dose, or with positive occult blood in the stool at baseline. If positive, it should be rechecked, and if still positive, clinical judgment should be made, including possible gastrointestinal endoscopy if necessary.
8. Patients who have received platelet or red blood cell transfusion within 14 days before starting treatment.
9. Patients with active ulcers, non-healing wounds, or fractures.
10. Patients who have experienced any severe bleeding event graded ≥2 in CTCAE 5.0 within 4 weeks before the first dose.
11. Patients with active infections or unexplained fever \>38.5°C during screening or before the first dose.
12. Patients with congenital or acquired immune deficiency (e.g., HIV-infected individuals) or active hepatitis (HBV reference: HBsAg positive, HBV DNA ≥500 IU/ml; HCV reference: HCV antibody positive, HCV RNA \> normal upper limit).
13. Patients who have previously received radiotherapy, chemotherapy, hormonal therapy, or molecular targeted therapy, with less than 4 weeks since the last dose of treatment (less than 5 half-lives for oral molecular-targeted agents); patients who have not recovered from treatment-related adverse events (except for hair loss) to ≤1 grade as per CTCAE 5.0.
14. Patients who have experienced arterial thrombosis or ≥grade 3 venous thromboembolic events within 6 months prior to the first dose, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, or pulmonary embolism.
15. Patients with a history of hereditary or acquired bleeding disorders or coagulation dysfunction (e.g., hemophilia, platelet dysfunction, thrombocytopenia, etc.).
16. Patients who may receive other systemic antitumor treatments during the study period.
17. Patients with uncontrolled hypertension, despite antihypertensive treatment (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg).
18. Pregnant or breastfeeding women, or women planning pregnancy during the study treatment.
19. Patients with other factors, as judged by the investigator, that may lead to the premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring concurrent treatment, severe laboratory abnormalities, or factors related to family or social circumstances that may impact the patient's safety, or the collection of data and samples.

Where this trial is running

Jinan, Shandong

• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)

Study contacts

• Principal investigator: Beihua Kong — Qilu Hospital of Shandong University
• Study coordinator: Hualei Bu

Conditions Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer