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

Official title

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

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.

Interventions

• 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.
• 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.
• Drug PARPi
  For patients with gBRCA/sBRCA mutation and CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors.

Primary outcome measures

• Overall survival [Time frame: Participants will be followed for at least 5 years after randomization]

Secondary outcome measures (8)

• Progression-free survival [Time frame: Participants will be followed for at least 2 years after randomization]
• Post-operative complications [Time frame: Participants will be followed up to 3 months after randomization]
• Quality of life assessments [Time frame: Participants will be followed for at least 12 months or death after randomization, whichever came first]
• Quality of life assessments [Time frame: Participants will be followed for at least 12 months or death after randomization, whichever came first]
• Accumulating treatment-free survival [Time frame: Participants will be followed for at least 5 years or death after randomization, whichever came first]
• Time to first subsequent anticancer therapy [Time frame: Participants will be followed for at least 2 years or death after randomization, whichever came first]
• Time to secondary subsequent anticancer therapy [Time frame: Participants will be followed for at least 5 years or death after randomization, whichever came first]
• Progression-free survival 2 [Time frame: Participants will be followed for at least 5 years or death after randomization, whichever came first]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Zhongshan Hospital Fudan University — Shanghai
• Obstetrics & Gynecology Hospital of Fundan University — Shanghai
• Shanghai First Maternity and Infant Hospital — Shanghai
• Shanghai Jiao Tong University School of Medicine Xinhua Hospital — Shanghai

Identifiers

NCT: NCT04515602 · FOCUS · SOC-4 · SGOG-OV6

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗