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

Phase 2

Recruiting

• Conditions: Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Ovarian Cancer
• Interventions: Procedure: Primary debulking surgery; Procedure: Neoadjuvant chemotherapy; Drug: PARP inhibitor; Drug: Bevacizumab

• Registration Number: NCT05200260
• Lead Sponsor: Shanghai Gynecologic Oncology Group

Brief Summary

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

Detailed Description

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

Study Timeline

• Study First Submitted: 2022-01-17
• Study First Submitted QC: 2022-01-17
• Study First Posted: 2022-01-20
• Study Start: 2022-07-13
• Status Verified: 2024-11
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-10
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 220

Inclusion Criteria

• Females aged ≥ 18 years.

• Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma

• Low, Middle tumor burden and high tumor burden with cPCI score ≤ 12 based on pre-operative CT or PET/CT examination

• Complete cytoreduction can be achieved based on CT or PET/CT examination

• Patients must agree to undergo BRCA (breast cancer gene) and HRD (homologous recombination deficiency) testing

• Performance status (ECOG 0-2)

• Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery:

  1. white blood cells >3,000/µL, absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL, hemoglobin ≥9 g/dL,
  2. 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,
  3. 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 olaparib/bevacizumab or its excipients
• Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ, thyroid carcinoma, or breast carcinoma (without any signs of relapse or activity, early-stage).
• Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise adherence to the protocol.
• Other conditions, such as religious, psychological, and other factors, that could interfere with the provision of informed consent, compliance to study procedures, or follow-up.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Upfront cytoreductive surgery with maintenance therapy	Primary debulking surgery	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).
Upfront cytoreductive surgery with maintenance therapy	PARP inhibitor	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).
Upfront cytoreductive surgery with maintenance therapy	Bevacizumab	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).
Neoadjuvant chemotherapy with maintenance therapy	Neoadjuvant chemotherapy	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).
Neoadjuvant chemotherapy with maintenance therapy	PARP inhibitor	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).
Neoadjuvant chemotherapy with maintenance therapy	Bevacizumab	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 (patients with or without BRCA mutation will be maintained by PARPi or Bevacizumab respectively ).

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)
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
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)
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
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
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.

Trial Locations

Locations (9)

The First People's Hospital of Foshan; 🇨🇳 Foshan, China

Sun Yet-Sen University Cancer Center; 🇨🇳 Guangzhou, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, China

The First Affiliated Hospital of University of Science and Technology of China; 🇨🇳 Hefei, China

Fudan University Cancer Hospital; 🇨🇳 Shanghai, China

Obstetrics and Gynecology Hospital of Fundan University; 🇨🇳 Shanghai, China

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, China