Clinical trial NCT04515602: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Lead sponsor: Shanghai Gynecologic Oncology Group
Sponsor class: OTHER_GOV
Collaborators: name: Obstetrics & Gynecology Hospital of Fudan University
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai First Maternity and Infant Hospital
First posted: 2020-08-17
Enrollment: 410
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: For Part 1:

Inclusion Criteria:

1. Females aged ≥ 18 years.
2. 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:

   1. the patient has a pelvic mass, and
   2. omental cake or other metastasis larger than 2 cm in the upper abdomen, or pathologic confirmed extra-abdominal metastasis (FIGO IV), and
   3. preoperative CA125/CEA ratio \> 25. If CA125/CEA ratio ≤ 25, imaging or endoscopy is obligatory to exclude a primary gastric, colon, or breast carcinoma.
3. cPCI score ≤ 8.
4. Performance status (ECOG 0-2).
5. Good ASA score (1/2).
6. 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.
7. Comply with the study protocol and follow-up.
8. Patients who have given their written informed consent.

Exclusion Criteria:

1. Non-epithelial ovarian malignancies and borderline tumors.
2. Low grade ovarian cancer.
3. Mucinous ovarian cancer.
4. cPCI score \> 8.
5. Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ or breast carcinoma (without any signs of relapse or activity).
6. Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise the adherence to the protocol.
7. 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:

1. Females aged ≥ 18 years, and \< 70 years.
2. Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma.
3. cPCI score ≥ 10.
4. 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.
5. Good performance status (ECOG 0-1).
6. Good ASA score (1/2).
7. Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery.
8. Comply with the study protocol and follow-up.
9. Patients who have given their written informed consent.

Exclusion Criteria:

1. Non-epithelial ovarian malignancies and borderline tumors.
2. Low grade ovarian cancer.
3. Mucinous ovarian cancer.
4. Clear cell carcinoma.
5. cPCI score \< 8.
6. Lung metastasis, diffused pleural metastasis, bone metastasis, metastasis of mediastinal lymph node, internal mammary node, or multiple extra-peritoneal lymph nodes.
7. Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ or breast carcinoma (without any signs of relapse or activity).
8. Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise the adherence to the protocol.
9. Other conditions, such as religious, psychological and other factors, that could interfere with provision of informed consent, compliance to study procedures, or follow-up.

Primary outcomes:
measure: Overall survival
timeFrame: Participants will be followed for at least 5 years after randomization
Secondary outcomes:
measure: Progression-free survival
timeFrame: Participants will be followed for at least 2 years after randomization
measure: Post-operative complications
timeFrame: Participants will be followed up to 3 months after randomization
measure: Quality of life assessments
timeFrame: Participants will be followed for at least 12 months or death after randomization, whichever came first
measure: Quality of life assessments
timeFrame: Participants will be followed for at least 12 months or death after randomization, whichever came first
measure: Accumulating treatment-free survival
timeFrame: Participants will be followed for at least 5 years or death after randomization, whichever came first
measure: Time to first subsequent anticancer therapy
timeFrame: Participants will be followed for at least 2 years or death after randomization, whichever came first
measure: Time to secondary subsequent anticancer therapy
timeFrame: Participants will be followed for at least 5 years or death after randomization, whichever came first
measure: Progression-free survival 2
timeFrame: Participants will be followed for at least 5 years or death after randomization, whichever came first
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fundan University
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine Xinhua Hospital
Study officials:
References: