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

NCT ID: NCT04515602

Last Updated: 2020-08-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-31
• Study Completion Date: 2028-01-31

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.

Conditions

Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Arm I (low/medium tumor burden)

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.

Group Type: EXPERIMENTAL

Primary debulking surgery

Intervention Type: PROCEDURE

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.

PARPi

Intervention Type: DRUG

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

Part 1 Arm II (low/medium tumor burden)

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.

Group Type: ACTIVE_COMPARATOR

Neoadjuvant chemotherapy

Intervention Type: PROCEDURE

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.

PARPi

Intervention Type: DRUG

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

Part 2 Arm I (high tumor burden)

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.

Group Type: EXPERIMENTAL

Primary debulking surgery

Intervention Type: PROCEDURE

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.

PARPi

Intervention Type: DRUG

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

Part 2 Arm II (high tumor burden)

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.

Group Type: ACTIVE_COMPARATOR

Neoadjuvant chemotherapy

Intervention Type: PROCEDURE

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.

PARPi

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

PARPi

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

Intervention Type: DRUG

Other Intervention Names

PDS; Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS

Eligibility Criteria

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.

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. 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:

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Obstetrics & Gynecology Hospital of Fudan University

OTHER

Sponsor Role: collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Shanghai First Maternity and Infant Hospital

OTHER

Sponsor Role: collaborator

Shanghai Gynecologic Oncology Group

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Obstetrics & Gynecology Hospital of Fundan University

Shanghai, , China

Shanghai First Maternity and Infant Hospital

Shanghai, , China

Shanghai Jiao Tong University School of Medicine Xinhua Hospital

Shanghai, , China

Countries

China

Central Contacts

Lina Shen, MD

Role: CONTACT

shen.lina@zs-hospital.sh.cn

86 21 64041990

Tingyu Luan

Role: CONTACT

luan.yuting@zs-hospital.sh.cn

86 21 64041990

Facility Contacts

Wei Jiang, MD, PhD

Role: primary

86 21 33189900

Xiaoqing Guo, MD, PhD

Role: primary

86 21 20261000

Xipeng Wang, MD, PhD

Role: primary

86 21 25078999

Other Identifiers

SOC-4

Identifier Type: REGISTRY

Identifier Source: secondary_id

SGOG-OV6

Identifier Type: REGISTRY

Identifier Source: secondary_id

FOCUS

Identifier Type: -

Identifier Source: org_study_id