Stratified Evaluation and Prediction of Survival Benefit for PDS or NACT-IDS in Advanced Ovarian Cancer, A Randomized, Phase 3 Trial After the SUNNY Study
Overview
- Phase
- Phase 3
- Intervention
- PARPi
- Conditions
- Epithelial Ovarian Cancer
- Sponsor
- Shanghai Gynecologic Oncology Group
- Enrollment
- 410
- Locations
- 4
- Primary Endpoint
- Overall survival
- Status
- Not yet recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to answer the fundamental question 'The Optimal Timing of Surgery' in advanced ovarian cancer patients with different tumor burden, and to perform translational study.
Detailed Description
OBJECTIVES: Compare the efficacy and safety in patients with advanced ovarian cancer treated with NACT-IDS versus PDS, among different tumor burden groups. Compare survival benefit of PARPi therapy in patients treated with PDS or NACT-IDS. OUTLINE: This is a randomized phase III multicenter study. Patients will receive upfront maximal cytoreductive surgery followed by at least 6 cycles of adjuvant chemotherapy or 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery, and then at least 3 cycles of adjuvant chemotherapy, and maintenance therapy of PARP inhibitor for patients with gBRCA/sBRCA mutation who had a complete or partial clinical response after platinum-based chemotherapy. Patients are followed every 3 months within the first 5 years, and then every 6 months. PROJECTED ACCRUAL: A total of 410 patients will be accrued for this study within 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Females aged ≥ 18 years.
- •Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma (diagnosis by biopsy or core needle biopsy\*, laparoscopic biopsy is not recommended). \* If core needle biopsy could not be performed, patients should satisfy the following conditions:
- •the patient has a pelvic mass, and
- •omental cake or other metastasis larger than 2 cm in the upper abdomen, or pathologic confirmed extra-abdominal metastasis (FIGO IV), and
- •preoperative CA125/CEA ratio \>
- •If CA125/CEA ratio ≤ 25, imaging or endoscopy is obligatory to exclude a primary gastric, colon, or breast carcinoma.
- •cPCI score ≤
- •Performance status (ECOG 0-2).
- •Good ASA score (1/2).
- •Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery:
Exclusion Criteria
- •Non-epithelial ovarian malignancies and borderline tumors.
- •Low grade ovarian cancer.
- •Mucinous ovarian cancer.
- •cPCI score \>
- •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.
- •For Part 2:
- •Inclusion Criteria:
- •Females aged ≥ 18 years, and \< 70 years.
Arms & Interventions
Part 2 Arm II (high tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: PARPi
Part 1 Arm I (low/medium tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: Primary debulking surgery
Part 1 Arm I (low/medium tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: PARPi
Part 1 Arm II (low/medium tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: Neoadjuvant chemotherapy
Part 1 Arm II (low/medium tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: PARPi
Part 2 Arm I (high tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: Primary debulking surgery
Part 2 Arm I (high tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: PARPi
Part 2 Arm II (high tumor burden)
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 gBRCA/sBRCA mutation, CR/PR after platinum-based therapy.
Intervention: Neoadjuvant chemotherapy
Outcomes
Primary Outcomes
Overall survival
Time Frame: Participants will be followed for at least 5 years after randomization
Time from randomization to the date of death from any cause or date of last contact
Secondary Outcomes
- Progression-free survival(Participants will be followed for at least 2 years after randomization)
- Post-operative complications(Participants will be followed up to 3 months after randomization)
- Quality of life assessments(Participants will be followed for at least 12 months or death after randomization, whichever came first)
- Accumulating treatment-free survival(Participants will be followed for at least 5 years or death after randomization, whichever came first)
- Time to first subsequent anticancer therapy(Participants will be followed for at least 2 years or death after randomization, whichever came first)
- Time to secondary subsequent anticancer therapy(Participants will be followed for at least 5 years or death after randomization, whichever came first)
- Progression-free survival 2(Participants will be followed for at least 5 years or death after randomization, whichever came first)