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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Procedure: Primary debulking surgery; Procedure: Neoadjuvant chemotherapy; Drug: PARPi

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 Type: Interventional
• Enrollment (Anticipated): 410
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lina Shen, MD; Phone Number: 86 21 64041990; Email: shen.lina@zs-hospital.sh.cn
• Study Contact Backup: Name: Tingyu Luan; Phone Number: 86 21 64041990; Email: luan.yuting@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China
    • Obstetrics & Gynecology Hospital of Fundan University
    • Contact: Wei Jiang, MD, PhD; Phone Number: 86 21 33189900
  • Shanghai, China
    • Shanghai first maternity and infant hospital
    • Contact: Xiaoqing Guo, MD, PhD; Phone Number: 86 21 20261000
  • Shanghai, China
    • Shanghai Jiao Tong University School of Medicine Xinhua Hospital
    • Contact: Xipeng Wang, MD, PhD; Phone Number: 86 21 25078999
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: PDS; Drug: PARPi; For patients with gBRCA/sBRCA mutation and CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors.
Active Comparator: 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.	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.; Other Names: Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS; Drug: PARPi; For patients with gBRCA/sBRCA mutation and CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors.
Experimental: 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.	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.; Other Names: PDS; Drug: PARPi; For patients with gBRCA/sBRCA mutation and CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors.
Active Comparator: 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.	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.; Other Names: Neoadjuvant chemotherapy followed by interval debulking surgery, NACT-IDS; Drug: PARPi; For patients with gBRCA/sBRCA mutation and CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to the date of death from any cause or date of last contact	Participants will be followed for at least 5 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative complications	The surgical complications will be evaluated at 30-day, 60-day, 90-day after upfront cytoreductive surgery or interval debulking surgery	Participants will be followed up to 3 months after randomization
Progression-free survival	Time from randomization to the date of first progressive disease or death, whichever occurs first or date of last contact	Participants will be followed for at least 2 years after randomization
Quality of life assessments	Quality of life (Qol) as measured by QOQ-C30	Participants will be followed for at least 12 months or death after randomization, whichever came first
Quality of life assessments	Quality of life (Qol) as measured by FACT-O	Participants will be followed for at least 12 months or death after randomization, whichever came first
Accumulating treatment-free survival	The overall survival time minus the total treatment time of surgery and chemotherapy after randomization, regardless of the targeted therapy	Participants will be followed for at least 5 years or death after randomization, whichever came first
Time to first subsequent anticancer therapy	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	Participants will be followed for at least 2 years or death after randomization, whichever came first
Time to secondary subsequent anticancer therapy	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	Participants will be followed for at least 5 years or death after randomization, whichever came first
Progression-free survival 2	Time from randomization to second progressive disease or death, which occurs first or date of last contact	Participants will be followed for at least 5 years or death after randomization, whichever came first

Collaborators and Investigators

• Sponsor: Shanghai Gynecologic Oncology Group
• Collaborators: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Obstetrics & Gynecology Hospital of Fudan University; Shanghai First Maternity and Infant Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 1, 2028
• Study Completion (Anticipated): January 1, 2028

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: FOCUS; SOC-4 (Registry Identifier: Shanghai Gynecologic Oncology Group); SGOG-OV6 (Registry Identifier: Shanghai Gynecologic Oncology Group)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No