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In this study, investigators propose to use fuzuloparib and apatinib as neoadjuvant therapy for Homologous recombination deficiency (HRD)positive advanced ovarian cancer patients, aiming to explore the efficacy and safety of this 'de-chemotherapy' regimen as neoadjuvant therapy for advanced ovarian cancer, and to conduct genetically related subgroup analyses, to guide the precision therapy and provide a new therapeutic option for HRD-positive patients with advanced ovarian cancer. To provide a new treatment option In order to increase the R0 resection rate of surgery and reduce chemotherapy resistance, thus improving the prognosis and prolonging the survival of patients.
This study is a single-arm, interventional, open-label, prospective clinical trial. Patients with advanced epithelial ovarian cancer (Federation of International of Gynecologists and Obstetricians,FIGO stage III-IV), who are not eligible for R0 resection or unable to tolerate surgery based on radiological assessment (Suidan score) or laparoscopic assessment (Fagotti score), and who are Homologous recombination deficiency (HRD)positive, will receive neoadjuvant therapy with fuzuloparib and apatinib for two cycles (28 days per cycle). After neoadjuvant treatment, patients who achieve complete or partial response according to radiological assessment will proceed to the surgical treatment phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| neoadjuvant therapy | Experimental | Participants will receive neoadjuvant therapy with fuzuloparib and apatinib for a total of two cycles (28 days per cycle). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neoadjuvant therapy with fuzuloparib in combination with apatinib | Drug | Neoadjuvant Treatment Period Fuzuloparib: 150 mg, twice daily, orally, either before or after meals. It is recommended to take it within 0.5 hours after breakfast and dinner. Continuous administration for 4 weeks constitutes one cycle, for a total of two cycles. Apatinib: 250 mg, once daily, orally, recommended to be taken within 0.5 hours after breakfast. Continuous administration for 4 weeks constitutes one cycle, for a total of two cycles. |
| Measure | Description | Time Frame |
|---|---|---|
| R0 Resection Rate | Proportion of patients with advanced epithelial ovarian cancer who are not R0 resectable at first diagnosis or who cannot tolerate surgery who undergo tumour cytoreduction to achieve R0 resection. | 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Remission Rate (ORR) | The proportion of patients whose tumor volume decreases by a predetermined amount and maintains this reduction for the minimum required duration. It is the sum of the complete response (CR) and partial response (PR) rates. In other words, ORR = CR + PR. | 24 months |
| Progression-Free Survival (PFS) |
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Inclusion Criteria:
ECOG performance status >2.
Hematological tests (no transfusions or hematopoietic growth factor use within 7 days prior to screening): Hemoglobin (Hb) ≥90 g/L. Absolute neutrophil count (ANC) ≥1.5×10⁹/L. Absolute lymphocyte count (LC) ≥0.5×10⁹/L. Platelet count (PLT) ≥100×10⁹/L. White blood cell count (WBC) ≥3.0×10⁹/L and ≤15×10⁹/L. Biochemical tests (no transfusions or albumin use within 7 days prior to screening): Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Alkaline phosphatase (ALP) ≤2.5×ULN. Total bilirubin (TBIL) ≤1.5×ULN.
Serum creatinine (Cr) ≤1.5×ULN, with creatinine clearance (CrCL) ≥60 mL/min (Cockcroft-Gault formula). Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN, with international normalized ratio (INR) ≤1.5×ULN (not receiving anticoagulant therapy).
Urinalysis: Urine protein <2+; if urine protein ≥2+, then 24-hour urine protein quantification must show protein ≤1 g. 12-lead electrocardiogram (ECG): Fridericia-corrected QT interval (QTcF) <470 ms for females.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bin Li Bin Li, PhD | Contact | 86+13801364117 | libin@cicams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College | Recruiting | Beijing | Beijing Municipality | 100021 | China |
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| Preoperative Period | Procedure | Discontinue Fuzuloparib 7 days before surgery. Discontinue Apatinib 14 days before surgery. The specific timing will be assessed by the investigator based on postoperative wound healing. |
|
| Chemotherapy | Drug | Postoperative Adjuvant Chemotherapy Period (≥4 cycles) Paclitaxel: 150-175 mg/m², intravenous infusion, every 3 weeks (Q3W). Carboplatin: AUC 4-5, intravenous infusion, every 3 weeks (Q3W). |
|
| Maintenance treatment | Drug | Maintenance Treatment Period Fuzuloparib: 150 mg, twice daily, orally. Continuous administration for 4 weeks constitutes one cycle. Treatment will continue until disease progression, intolerable toxicity, or other reasons as specified in the protocol. |
|
The time from randomization until tumor progression (as defined by RECIST 1.1 criteria) or death from any cause, whichever occurs first. |
| 24 months |
| Disease Control Rate (DCR) | The percentage of evaluable patients who achieve a response (PR + CR) or stable disease (SD) after treatment. Simply put, DCR = CR + PR + SD, according to the RECIST criteria for at least 4 weeks. | 24 months |
| Overall Survival (OS) | The time from randomization until death from any cause. For subjects who are lost to follow-up before death, the last follow-up time is usually counted as the time of death. | 36 months |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D020360 | Neoadjuvant Therapy |
| C553458 | apatinib |
| D057234 | Preoperative Period |
| D004358 | Drug Therapy |
| D058850 | Opiate Substitution Treatment |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D059035 | Perioperative Period |
| D013514 | Surgical Procedures, Operative |
| D005791 | Patient Care |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
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