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

Phase 3

Not yet recruiting

• Conditions: Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma
• Interventions: Procedure: Primary debulking surgery; Procedure: Neoadjuvant chemotherapy; Drug: PARPi

• Registration Number: NCT04515602
• Lead Sponsor: Shanghai Gynecologic Oncology Group

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.

Study Timeline

• Status Verified: 2020-08
• Study First Submitted: 2020-08-14
• Study First Submitted QC: 2020-08-14
• Study First Posted: 2020-08-17
• Last Update Submitted: 2020-08-25
• Last Update Posted: 2020-08-27
• Study Start: 2021-01
• Primary Completion: 2028-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 410

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1 Arm I (low/medium tumor burden)	Primary debulking surgery	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.
Part 1 Arm II (low/medium tumor burden)	PARPi	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.
Part 2 Arm I (high tumor burden)	Primary debulking surgery	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.
Part 2 Arm II (high tumor burden)	PARPi	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.
Part 1 Arm I (low/medium tumor burden)	PARPi	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.
Part 1 Arm II (low/medium tumor burden)	Neoadjuvant chemotherapy	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.
Part 2 Arm I (high tumor burden)	PARPi	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.
Part 2 Arm II (high tumor burden)	Neoadjuvant chemotherapy	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.

Primary Outcome Measures

Name	Time	Method
Overall survival	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 Outcome Measures

Name	Time	Method
Progression-free survival	Participants will be followed for at least 2 years after randomization	Time from randomization to the date of first progressive disease or death, whichever occurs first or date of last contact
Post-operative complications	Participants will be followed up to 3 months after randomization	The surgical complications will be evaluated at 30-day, 60-day, 90-day after upfront cytoreductive surgery or interval debulking surgery
Quality of life assessments	Participants will be followed for at least 12 months or death after randomization, whichever came first	Quality of life (Qol) as measured by FACT-O
Accumulating treatment-free survival	Participants will be followed for at least 5 years or death after randomization, whichever came first	The overall survival time minus the total treatment time of surgery and chemotherapy after randomization, regardless of the targeted therapy
Time to first subsequent anticancer therapy	Participants will be followed for at least 2 years or death after randomization, whichever came first	Time from the date of randomization to the starting date of the first subsequent anticancer therapy or death, whichever occurs first or date of last contact
Time to secondary subsequent anticancer therapy	Participants will be followed for at least 5 years or death after randomization, whichever came first	Time from the date of randomization to the starting date of the second subsequent anticancer therapy or death, whichever occurs first or date of last contact
Progression-free survival 2	Participants will be followed for at least 5 years or death after randomization, whichever came first	Time from randomization to second progressive disease or death, which occurs first or date of last contact

Trial Locations

Locations (4)

Obstetrics & Gynecology Hospital of Fundan University; 🇨🇳 Shanghai, China

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, Shanghai, China

Shanghai First Maternity and Infant Hospital; 🇨🇳 Shanghai, China

Shanghai Jiao Tong University School of Medicine Xinhua Hospital; 🇨🇳 Shanghai, China