Study of Upfront Surgery Versus Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer (SUNNY)

Study Overview
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Brief Summary
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The purpose of this study is to answer the fundamental question, should the physicians choose Surgery or Chemotherapy (SOC-2) in advanced ovarian cancer?

Detailed Description
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OBJECTIVES: Compare the efficacy and safety in patients with AJCC TNM stage IIIC or IV epithelial ovarian cancer, fallopian tube cancer, or peritoneal carcinoma treated with neoadjuvant chemotherapy followed by interval debulking surgery versus upfront surgery. 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. Patients are followed every 3 months within the first 5 years, and then every 6 months. PROJECTED ACCRUAL: A total of 488 patients will be accrued for this study within 5 years.

Official Title
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Study of Upfront Surgery Versus Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients With Stage IIIC and IV Ovarian Cancer

Conditions
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Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Procedure: Upfront cytoreductive surgery
* Procedure: Interval debulking surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥ 18 years. Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma (diagnosis by biopsy or fine needle aspiration*). Laparoscopic biopsy with pictures is recommended. * If fine needle aspiration showing an adenocarcinoma, patients should satisfy the following conditions: a. the patient has a pelvic mass, and b. omental cake or other metastasis larger than 2 cm in the upper abdomen, or pathologic confirmed extra-abdominal metastasis, and c. serum CA125/CEA ratio>25. If serum CA125/CEA ratio<25 or malignancies of other origins, such as breasts and digestive tract, are suspected from symptoms, physical examinations or imaging diagnosis, endoscopy or ultrasonography should be done to exclusive metastasis ovarian cancer. ECOG performance status of 0 to 2. ASA score of 1 to 2. Adequate bone marrow, liver and renal function to receive chemotherapy and subsequently to undergo 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. Written informed consent. Exclusion Criteria: Patients with non-epithelial tumors as well as borderline tumors. Mucinous ovarian cancer. Low grade ovarian cancer. Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ. 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<br>Upfront cytoreductive surgery with a maximal cytoreduction of complete gross resection within 3 weeks after biopsy, followed by at least 6 cycles of adjuvant chemotherapy. | Procedure: Upfront cytoreductive surgery<br>* Upfront cytoreductive 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: Primary debulking surgery, PDS;|
| Active Comparator: Neoadjuvant chemotherapy<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. | Procedure: Interval debulking surgery<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: NACT-IDS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The time from entry into the study to any cause of death. | Participants will be followed for at least 5 years after randomization or until death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The 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 5 years after randomization or until death | 
| Post-operative complications | The surgical complications will be evaluated at 30-day after upfront cytoreductive surgery or interval debulking surgery. | Participants will be followed up to 6 months after randomization | 
| Quality of life assessments | QOQ-C30,FACT-O( baseline; 6months, 12 months and 5 years after randomization) | Participants will be followed for at least 5 years after randomization or until death | 
| Accumulated treatment-free survival (TFSa) | The overall survival time minus the total treatment time of surgery and chemotherapy after randomization, but maintenance of targeted agents is considered off-treatment. | Participants will be followed for at least 5 years after randomization or until death | 
| Time to first subsequent anticancer therapy (TFST) | The date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurs first. Maintenance treatments following a cytostatic treatment are NOT considered separate treatment lines. | Participants will be followed for at least 5 years after randomization or until death | 
| Time to second subsequent anticancer therapy (TSST) | The date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurs first. Maintenance treatments following a cytostatic treatment are NOT considered separate treatment lines. | Participants will be followed for at least 5 years after randomization or until death | 
| 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 5 years after randomization or until death | 
| The rate of 5-year progression-free survival | The rate of the patients without progression or recurrence or death at 5 years. | Participants will be followed for at least 5 years after randomization or until death | 
| Outcomes of pulmonary embolism | The incidence of pulmonary embolism prior to primary treatment in the ITT and hospital populations. Its effect on survival between groups in the ITT and hospital populations. | Participants will be followed for at least 5 years after randomization or until death |