Fluzoparib with bevacizumab or a low‑carb dietary plan versus fluzoparib alone as first‑line maintenance for HRD‑positive and HRD‑negative advanced ovarian cancer

An Open-label, Randomized Controlled, Multicenter Study With Dual HRD-positive/Negative Cohorts Evaluating Fluzoparib Monotherapy Versus Combination Therapy With Bevacizumab or Dietary Intervention as Maintenance Treatment Following First-line Platinum-based Chemotherapy in Advanced Ovarian Cancer

This trial tests whether adding bevacizumab or a low‑carb dietary plan to fluzoparib helps women with advanced ovarian cancer, with or without HRD, remain free of cancer longer after first‑line treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 424 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, prednisone
• Locations: 2 sites (Wuhan, Hubei and 1 other locations)
• Trial ID: NCT06954584 on ClinicalTrials.gov

What this trial studies

This is a phase 3, first‑line maintenance trial conducted at Tongji Hospital that randomizes patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have known HRD status and completed platinum‑based chemotherapy. Patients with HRD‑positive tumors will be tested on fluzoparib plus bevacizumab compared with fluzoparib alone, while the HRD‑negative cohort will explore fluzoparib combined with a dietary (low‑carbohydrate) intervention versus fluzoparib monotherapy. Primary outcomes focus on survival measures such as progression‑free survival and safety/tolerability, with secondary outcomes likely including overall survival and quality of life. The design aims to confirm benefit in HRD‑positive patients and to see if a dietary approach can sensitize HRD‑negative tumors to PARP inhibition.

Who should consider this trial

Good fit: Adult women (≥18 years) with high‑grade serous, fallopian tube, primary peritoneal, or grade ≥II endometrioid ovarian cancer, FIGO stage III/IV, documented HRD status, and who have completed the required platinum‑based chemotherapy are the intended participants.

Not a fit: Patients who cannot tolerate bevacizumab, cannot adhere to the dietary intervention, or have medical conditions that preclude study treatments or follow‑up are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could extend the time without disease progression for women with advanced ovarian cancer and potentially offer a non‑drug strategy to improve response in HRD‑negative tumors.

How similar studies have performed: Previous trials have shown that PARP inhibitors and combinations with anti‑angiogenic agents can improve outcomes in ovarian cancer, while dietary sensitization of PARP resistance remains largely preclinical and early‑stage.

Eligibility criteria

Inclusion Criteria:

1. The participant voluntarily joins the study, provides written informed consent, demonstrates good compliance, and agrees to follow-up.
2. Female, age ≥18 years (calculated on the day of signing the informed consent form).
3. Histologically confirmed high-grade serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer ; endometrioid adenocarcinoma of the ovary (grade ≥II) :

   For mixed tumors: The high-grade serous or grade ≥II endometrioid component must exceed 50% .
4. FIGO 2018 staging as Stage III or IV .
5. Documented HRD (Homologous Recombination Deficiency) test results .
6. Completed platinum-based chemotherapy with the following requirements:

   * Patients unable to tolerate chemotherapy for definitive reasons must complete at least 4 cycles of platinum-based chemotherapy .
   * Patients undergoing interval debulking surgery must complete at least 3 cycles of platinum-based chemotherapy post-surgery .
7. Prior to randomization, patients must have no evidence of disease (NED) or achieve complete response (CR) or partial response (PR) after first-line platinum-based chemotherapy, with response maintained until study treatment initiation. Randomization and treatment must begin within 8 weeks after the last chemotherapy dose .

   -CR definition : No radiologic evidence of disease and CA125 ≤ upper limit of normal (ULN).

   -PR definition : ≥30% reduction in tumor size compared to pre-chemotherapy or CA125 reduction ≥90% from baseline (if imaging shows no lesions but CA125 remains above ULN).

   -For patients achieving NED after initial debulking surgery:CA125 must decrease to \<1×ULN during treatment and remain \<1×ULN within 7 days prior to randomization; or CA125 reduction ≥90% from baseline and no \>10% increase within 7 days prior to randomization.

   -Prohibited during/after platinum-based chemotherapy : Concurrent use of other investigational drugs (except endocrine therapy) or treatments.

   -Permitted during chemotherapy : Bevacizumab combination therapy.
8. ECOG Performance Status (PS) : 0-1.
9. Adequate organ function (no blood transfusions or growth factors within 14 days prior to randomization):

   -Absolute neutrophil count (ANC) ≥1.5×10⁹/L.

   -Platelets ≥90×10⁹/L.

   -Hemoglobin ≥9 g/dL.

   -Serum albumin ≥3 g/dL.

   -Total bilirubin ≤1.5×ULN.

   -ALT and AST ≤2.5×ULN.
   * Serum creatinine ≤1.5×ULN.

     1 0.For women of childbearing potential :
   * Negative serum pregnancy test within 72 hours prior to randomization.
   * Agreement to use medically approved contraception during treatment and for 6 months after the last dose .
   * Non-lactating.

   Additional Inclusion Criteria for HRD-Negative Cohort Only :

11\. Baseline body mass index (BMI) ≥18.5 kg/m² (BMI = weight \[kg\]/height \[m\]²).

Exclusion Criteria:

1. History of other untreated or active malignancies within 5 years (except cured thyroid cancer, basal cell carcinoma, cervical carcinoma in situ, or breast cancer with \>3 years of recurrence-free survival after radical surgery).
2. Untreated central nervous system (CNS) metastases :

   -Patients with stable CNS metastases (confirmed by imaging for ≥1 month) after prior systemic/local therapy (e.g., surgery/radiotherapy) and off steroids (\>10 mg/day prednisone equivalent) for \>2 weeks may be eligible.
3. Prior use of PARP inhibitors (e.g., olaparib, niraparib, rucaparib, pamiparib, fluzoparib).

4 .Inability to swallow tablets or gastrointestinal dysfunction affecting drug absorption (per investigator judgment).

5.Bowel obstruction or gastrointestinal perforation within 3 months prior to randomization.

6.Symptomatic malignant ascites/pleural effusion requiring drainage or drainage within 3 months prior to randomization.

7.Poorly controlled cardiac disease :

* NYHA Class ≥II heart failure.
* Unstable angina.
* Myocardial infarction within 1 year.
* Clinically significant arrhythmias requiring treatment.
* QTc interval \>470 ms. 8.Coagulation abnormalities :
* INR \>1.5 or PT \>ULN +4 seconds.
* Bleeding tendency or current use of thrombolytics/anticoagulants (low-dose LMWH or aspirin prophylaxis permitted).

  9.Clinically significant bleeding within 3 months prior to randomization (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer, vasculitis).
* If baseline fecal occult blood test is positive, retesting is required. Persistent positivity may necessitate endoscopy.

  10.Active ulcers, unhealed wounds, or fractures . 11.Uncontrolled hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg despite medication).

  1 2.Grade ≥2 bleeding events (per CTCAE v5.0) within 4 weeks prior to randomization.

  13.Active infection or unexplained fever \>38.5°C during screening/prior to randomization.

  14.Immunodeficiency or active hepatitis :
* HIV-positive.
* Active HBV (HBsAg+ and HBV DNA ≥500 IU/mL) or HCV (HCV Ab+ and HCV RNA \>ULN).

  1 5.Recent anticancer therapy :
* Chemotherapy, radiotherapy, hormonal therapy, or targeted therapy within 4 weeks prior to study treatment (or 5 half-lives for oral targeted agents).
* Residual toxicity from prior therapy \>Grade 1 (CTCAE v5.0; alopecia excluded). 16.Arterial/venous thromboembolism within 6 months prior to randomization (e.g., stroke, transient ischemic attack, DVT, pulmonary embolism).

  17.Hereditary/acquired bleeding disorders (e.g., hemophilia, thrombocytopenia).

  18.Planned use of other systemic anticancer therapies during the study. 19.Any condition that, per investigator judgment, may lead to premature study termination.

Additional Exclusion Criteria for HRD-Negative Cohort Only :

20\. Unintentional weight loss ≥5% within 3-6 months or presence of cachexia .

21\. Nutritional risk :

-NRS2002 score ≥3 or need for nutritional support. 22.Diabetes requiring insulin or insulin secretagogues . 23.Acute liver disease/dysfunction . 24.Active chronic or acute kidney disease/dysfunction

Where this trial is running

Wuhan, Hubei and 1 other locations

• Tongji Hospital — Wuhan, Hubei, China (Recruiting)
• Tongji Hospital — Wuhan, Hubei, China (Recruiting)

Conditions Ovarian Cancer