Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

Study Overview
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Brief Summary
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Optimal Timing of Surgery combined with Maintenance Therapy in the Front-line Treatment of Advanced Ovarian Cancer

Detailed Description
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The purpose of this trial is to answer the fundamental question 'The Optimal Timing of Surgery' combined with Poly-adenosine Ribose Phosphate Inhbitors (PARPi), in the circumstance of primarily diagnosed advanced epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma.

Official Title
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A Prospective, Multicenter, Randomized Phase II Trial on Optimal Timing of Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Procedure: Primary debulking surgery
* Procedure: Neoadjuvant chemotherapy
* Drug: PARP inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged ≥ 18 years. Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma Middle tumor burden and high tumor burden with cPCI score ≤ 12 based on pre-operative PET/CT examination Complete cytoreduction can be achieved based on PET/CT examination Patients must agree to undergo BRCA (breast cancer gene) and HRD (homologous recombination deficiency) testing Performance status (ECOG 0-2) Good ASA score (1/2) Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery: white blood cells >3,000/µL, absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL, hemoglobin ≥9 g/dL, serum creatinine <1.25 x upper normal limit (UNL) or creatinine clearance ≥60 mL/min according to Cockroft-Gault formula or to local lab measurement, serum bilirubin <1.25 x UNL, AST(SGOT) and ALT(SGPT) <2.5 x UNL. Comply with the study protocol and follow-up. Patients who have given their written informed consent. Exclusion Criteria: Non-epithelial ovarian malignancies and borderline tumors Low grade ovarian cancer Mucinous ovarian cancer Complete cytoreduction cannot be achieved according to preoperative evaluation, including pulmonary and hepatic parenchymal metastases, unresectable extensive pleural metastases, multiple thoracic lymph nodes metastases, brain or bone metastases Patient has a known hypersensitivity to the components of niraparib or its excipients Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ or breast carcinoma (without any signs of relapse or activity). Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise the adherence to the protocol. Other conditions, such as religious, psychological and other factors, that could interfere with provision of informed consent, compliance to study procedures, or follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upfront cytoreductive surgery with maintenance therapy<br>Primary debulking surgery with a maximal cytoreduction of complete gross resection within 3 weeks after biopsy, followed by at least 6 cycles of adjuvant chemotherapy and maintenance therapy for patients with CR/PR after platinum-based therapy. | Procedure: Primary debulking surgery<br>* Primary debulking surgery with a maximum cytoreduction, then followed by 6 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5.<br>* Other names: PDS;Drug: PARP inhibitor<br>* For patients with CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors. In this trial, Niraparib 200mg po qd is suggested after the front-line therapy.<br>* Other names: Niraparib;|
| Active Comparator: Neoadjuvant chemotherapy with maintenance therapy<br>Neoadjuvant chemotherapy with 3 cycles of chemotherapy, then followed by interval debulking surgery. The maximal time interval between course 3 chemotherapy and IDS is 6 weeks. And then 3 cycles of adjuvant chemotherapy and maintenance therapy for patients with CR/PR after platinum-based therapy. | Procedure: Neoadjuvant chemotherapy<br>* 3 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5, Interval debulking surgery with a maximal cytoreduction of complete gross resection, then followed by another 3 cycles of chemotherapy.<br>* Other names: Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS;Drug: PARP inhibitor<br>* For patients with CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors. In this trial, Niraparib 200mg po qd is suggested after the front-line therapy.<br>* Other names: Niraparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival | The proportion of patients alive at 3 years after entry into the study | Participants will be followed for at least 3 years after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from entry into the study to any cause of death | Participants will be followed for at least 3 years after randomization | 
| Progression-free survival | Time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first | Participants will be followed for at least 3 years after randomization | 
| Post-operative complications | The surgical complications will be evaluated at 30-day, 60-day, 90-day after upfront cytoreductive surgery or interval debulking surgery | Participants will be followed up to 3 months after randomization | 
| Quality of life assessments | QLQ-C30, FACT-Q (baseline; 6 months, 12 months, 24 months and 36 months after randomization) | Participants will be followed for at least 3 years after randomization | 
| Accumulated treatment-free survival | Time from the date of randomization to death from any reason, minus the total treatment time of surgery and chemotherapy after randomization (regardless of targeted therapy) | Participants will be followed for at least 3 years or death after randomization | 
| TFST | Time from the date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurred first, whichever occurred first | Participants will be followed for at least 3 years or death after randomization | 
| TSST | Time from the date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurred first | Participants will be followed for at least 3 years or death after randomization | 
| The pattern of the first relapse | The number and sites of the first relapse, including pelvic, abdominal, retroperitoneal lymph nodes, distant metastases and ascites will be compared between the two groups. | Participants will be followed for at least 3 years or death after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Poly-adenosine Ribose Phosphate Inhbitors (PARPi), Ovarian Cancer, Primary Debulking Surgery, Neoadjuvant chemotherapy