Stratified Evaluation of PDS and NACT-IDS in Ovarian Cancer (FOCUS)

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.

For Part 1:

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 > 25. If CA125/CEA ratio ≤ 25, imaging or endoscopy is obligatory to exclude a primary gastric, colon, or breast carcinoma.
• cPCI score ≤ 8.
• 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.
• cPCI score > 8.
• 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.
• Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma.
• cPCI score ≥ 10.
• For FIGO IVB patients, abdominal lesions should be confined to one lobe of liver parenchyma metastasis or splenic metastasis. All extra-abdominal metastases should be resectable, such as inguinal lymph nodes, solitary supraclavicular, retrocrural or paracardial nodes.
• Good performance status (ECOG 0-1).
• Good ASA score (1/2).
• Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery.
• 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.
• Clear cell carcinoma.
• cPCI score < 8.
• Lung metastasis, diffused pleural metastasis, bone metastasis, metastasis of mediastinal lymph node, internal mammary node, or multiple extra-peritoneal lymph nodes.
• 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.