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

Sponsor

Shanghai Gynecologic Oncology Group (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05200260

Collaborator

Fudan University (Other)

207

Enrollment

Location

Arms

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma	Procedure: Primary debulking surgery Procedure: Neoadjuvant chemotherapy Drug: PARP inhibitor	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

207 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Feb 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Upfront cytoreductive surgery with maintenance therapy 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 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. Other Names: PDS Drug: PARP inhibitor 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. Other Names: Niraparib
Active Comparator: Neoadjuvant chemotherapy with maintenance therapy 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 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. Other Names: Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS Drug: PARP inhibitor 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. Other Names: Niraparib

Arm

Intervention/Treatment

Experimental: Upfront cytoreductive surgery with maintenance therapy

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

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.

Other Names:

PDS

Drug: PARP inhibitor

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.

Other Names:

Niraparib

Active Comparator: Neoadjuvant chemotherapy with maintenance therapy

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

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.

Other Names:

Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS

Drug: PARP inhibitor

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.

Other Names:

Niraparib

Outcome Measures

Primary Outcome Measures

3-year overall survival [Participants will be followed for at least 3 years after randomization]
The proportion of patients alive at 3 years after entry into the study

Secondary Outcome Measures

Overall survival [Participants will be followed for at least 3 years after randomization]
Time from entry into the study to any cause of death
Progression-free survival [Participants will be followed for at least 3 years after randomization]
Time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first
Post-operative complications [Participants will be followed up to 3 months after randomization]
The surgical complications will be evaluated at 30-day, 60-day, 90-day after upfront cytoreductive surgery or interval debulking surgery
Quality of life assessments [Participants will be followed for at least 3 years after randomization]
QLQ-C30, FACT-Q (baseline; 6 months, 12 months, 24 months and 36 months after randomization)
Accumulated treatment-free survival [Participants will be followed for at least 3 years or death after randomization]
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)
TFST [Participants will be followed for at least 3 years or death after randomization]
Time from the date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurred first, whichever occurred first
TSST [Participants will be followed for at least 3 years or death after randomization]
Time from the date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurred first
The pattern of the first relapse [Participants will be followed for at least 3 years or death after randomization]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.