Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

A Prospective, Multicenter, Randomized Phase II Trial on Optimal Timing of Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

Optimal Timing of Surgery combined with Maintenance Therapy in the Front-line Treatment of Advanced Ovarian Cancer

Study Overview

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

Detailed Description

The purpose of this trial is to answer the fundamental question 'The Optimal Timing of Surgery' combined with Poly-adenosine Ribose Phosphate Inhbitors (PARPi), in the circumstance of primarily diagnosed advanced epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 207
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Libing Xiang; Phone Number: 2801 86 21 64041990; Email: xiang.libing@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China
    • 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

Inclusion Criteria:

• Females aged ≥ 18 years.
• Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma
• Middle tumor burden and high tumor burden with cPCI score ≤ 12 based on pre-operative PET/CT examination
• Complete cytoreduction can be achieved based on PET/CT examination
• Patients must agree to undergo BRCA (breast cancer gene) and HRD (homologous recombination deficiency) testing
• Performance status (ECOG 0-2)
• Good ASA score (1/2)

• 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.
• 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
• Complete cytoreduction cannot be achieved according to preoperative evaluation, including pulmonary and hepatic parenchymal metastases, unresectable extensive pleural metastases, multiple thoracic lymph nodes metastases, brain or bone metastases
• Patient has a known hypersensitivity to the components of niraparib or its excipients
• 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.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upfront cytoreductive surgery with maintenance therapy; 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 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: PARP inhibitor; For patients with CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors. In this trial, Niraparib 200mg po qd is suggested after the front-line therapy.; Other Names: Niraparib
Active Comparator: Neoadjuvant chemotherapy with maintenance therapy; 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 CR/PR after platinum-based therapy.	Drug: PARP inhibitor; For patients with CR/PR after first-line chemotherapy, maintenance therapy of PARP inhibitors. In this trial, Niraparib 200mg po qd is suggested after the front-line therapy.; Other Names: Niraparib; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year overall survival	The proportion of patients alive at 3 years after entry into the study	Participants will be followed for at least 3 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from entry into the study to any cause of death	Participants will be followed for at least 3 years after randomization
Progression-free survival	Time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first	Participants will be followed for at least 3 years after randomization
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
Quality of life assessments	QLQ-C30, FACT-Q (baseline; 6 months, 12 months, 24 months and 36 months after randomization)	Participants will be followed for at least 3 years after randomization
Accumulated treatment-free survival	Time from the date of randomization to death from any reason, minus the total treatment time of surgery and chemotherapy after randomization (regardless of targeted therapy)	Participants will be followed for at least 3 years or death after randomization
TFST	Time from the date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurred first, whichever occurred first	Participants will be followed for at least 3 years or death after randomization
TSST	Time from the date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurred first	Participants will be followed for at least 3 years or death after randomization
The pattern of the first relapse	The number and sites of the first relapse, including pelvic, abdominal, retroperitoneal lymph nodes, distant metastases and ascites will be compared between the two groups.	Participants will be followed for at least 3 years or death after randomization

Collaborators and Investigators

• Sponsor: Shanghai Gynecologic Oncology Group
• Collaborators: Fudan University
• Investigators: Study Chair: Libing Xiang, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): February 1, 2027
• Study Completion (Anticipated): February 1, 2027

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: January 17, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Ovarian Cancer; Neoadjuvant chemotherapy; Primary Debulking Surgery; Poly-adenosine Ribose Phosphate Inhbitors (PARPi)
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Niraparib; Poly(ADP-ribose) Polymerase Inhibitors
• Other Study ID Numbers: SAT-1

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