Fluzoparib With or Without Bevacizumab for Neoadjuvant Therapy in Advanced Ovarian Cancer

NCT06735326 | Recruiting Phase 2

• 1 other identifier: KYLL-202410-008-1
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, open-label, multi-cohort, multicenter clinical trial, aimed at evaluating the efficacy and safety of Fluzoparib monotherapy, Fluzoparib in combination with Bevacizumab, and standard chemotherapy (Paclitaxel plus Carboplatin) as neoadjuvant treatments in newly diagnosed, germline BRCA1/2-mutated epithelial ovarian cancer patients (FIGO stage III/IV). The study also aims to assess the efficacy and safety of Fluzoparib as maintenance therapy following surgery and chemotherapy. The primary endpoint of the study is the objective response rate (ORR) for neoadjuvant therapy, as assessed by the investigator using RECIST v1.1 criteria. Secondary endpoints include R0 resection rate, overall survival (OS), and progression-free survival (PFS). The study will also evaluate the safety, tolerability, and patient-reported outcomes (EQ-5D-5L) across the three treatment cohorts.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The percentage of patients who achieve a complete response (CR) or partial response (PR) as determined by the investigator based on RECIST v1.1 criteria, at the end of neoadjuvant treatment.

  At the end of neoadjuvant treatment. The Fluzoparib monotherapy and Fluzoparib plus Bevacizumab groups will receive 2 cycles of treatment (28 days per cycle). The Paclitaxel plus Carboplatin group will receive 3 cycles of treatment (21 days per cycle).

Secondary Outcomes (6)

• R0 resection rate

  Immediately after final interval debulking surgery.

• pCR

  Post-surgical pathology (up to 2 weeks post surgery).

• Overall survival (OS)

  The time from patient enrollment until the date of death from any cause, assessed up to 120 months.

• Progression free survival (PFS)

  The time from patient enrollment until the date of first documented tumor progression or death from any cause, whichever occurs first, assessed up to 60 months.

• Safety evaluation

  From the start of neoadjuvant therapy to the end of maintenance therapy, assessed up to 30 months.

Study Arms (3)

Fluzoparib monotherapy

EXPERIMENTAL

Fluzoparib capsules with a treatment cycle of 28 days, for a total of 2 cycles.

Drug: Fluzoparib

Fluzoparib in combination with Bevacizumab

EXPERIMENTAL

Fluzoparib capsules with a treatment cycle of 28 days, for a total of 2 cycles; in combination with Bevacizumab injection (7.5mg/kg, intravenous infusion, administered once every three weeks), for a total of 2 doses.

Drug: Fluzoparib; Drug: Bevacizumab

Paclitaxel plus Carboplatin

ACTIVE COMPARATOR

Paclitaxel injection plus Carboplatin injection, administered once every three weeks for a total of 3 doses. If there is an allergy to Paclitaxel, it is recommended to replace it with Docetaxel or Liposomal Doxorubicin.

Drug: Paclitaxel; Drug: Carboplatin

Interventions

Fluzoparib DRUG

Fluzoparib capsule (50mg per capsule) 150mg po BID

Fluzoparib in combination with Bevacizumab; Fluzoparib monotherapy

Bevacizumab DRUG

Bevacizumab injection (100mg per vial) 7.5mg/kg ivdrip Q3W

Fluzoparib in combination with Bevacizumab

Paclitaxel DRUG

Paclitaxel injection 135-175mg/㎡ ivdrip Q3W

Paclitaxel plus Carboplatin

Carboplatin DRUG

Carboplatin injection AUC=4-5 ivdrip Q3W

Paclitaxel plus Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject voluntarily agrees to participate and signs the informed consent form.
• Age ≥18 years (calculated as of the date of signing the informed consent).
• 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%.
• The subject has at least one measurable lesion that can be assessed by CT or MRI (RECIST v1.1).
• 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.
• Expected survival \>12 weeks.
• ECOG performance status: 0-2.
• Confirmed germline BRCA1/2 mutations by professional genetic testing.
• Function of major organs meets the following requirements (no blood products or colony-stimulating factors allowed within 14 days prior to the first dose):
• Absolute neutrophil count ≥1.5 × 10\^9/L.
• Platelet count ≥100 × 10\^9/L.
• Hemoglobin ≥9 g/dL.
• Serum albumin ≥3 g/dL.

You may not qualify if:

• 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.
• 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.
• Patients who have previously received treatment with known or potential PARP inhibitors or Bevacizumab.
• Patients unable to swallow tablets or with gastrointestinal dysfunction that may affect drug absorption, as judged by the investigator.
• Patients who have experienced bowel obstruction or gastrointestinal perforation within the last 3 months.
• Patients with poorly controlled heart conditions or diseases, such as:
• NYHA Class II or higher heart failure.
• Unstable angina.
• Myocardial infarction within 1 year.
• Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• QTc \>470 ms.
• 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.
• Patients who have received platelet or red blood cell transfusion within 14 days before starting treatment.
• Patients with active ulcers, non-healing wounds, or fractures.
• Patients who have experienced any severe bleeding event graded ≥2 in CTCAE 5.0 within 4 weeks before the first dose.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250000, China

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

fluzoparib; Bevacizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Beihua Kong

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

• Kun Song

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hualei Bu

CONTACT

(+86)0531-82165881; buhualei@email.sdu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: December 16, 2024
• Study Start: November 27, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

CN (1)