Surgery and Niraparib in Secondary Recurrent Ovarian Cancer (SOC-3 Trial)

Study Overview
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Brief Summary
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This is a Phase II, open-label, multicenter, randomized umbrella study to evaluate the efficacy of cytoreductive surgery and Niraparib maintenance in participants with platinum-sensitive secondary recurrent ovarian cancer. Cohort 1 will focus on participants without prior use of PARP inhibitor, and without prior secondary cytoreduction (SCR) when first recurrence. Cohort 2 will focus on participants with prior use of PARP inhibitor, but without prior SCR when first recurrence. Cohort 3 will focus on participants with SCR when first recurrence, but without prior use of PARP inhibitor.

Detailed Description
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This exploratory trial is to compare the efficacy of secondary cytoreductive surgery followed by chemotherapy and Niraparib maintenance, versus chemotherapy alone followed by Niraparib maintenance in patients with platinum-sensitive secondary recurrent ovarian cancer.

Official Title
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A Phase II, Randomized Study of Cytoreductive Surgery Combined With Niraparib Maintenance in Platinum-sensitive, Secondary Recurrent Ovarian Cancer

Conditions
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Ovarian Cancer Recurrent, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Procedure: Surgery
* Drug: carboplatin/taxane, carboplatin/gemcitabine, cisplatin/gemcitabine, liposome doxorubicin/carboplatin...
* Drug: Niraparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years to ≤ 75 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Patients with platinum-sensitive, secondary relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. Front-line or second-line treatment may have included maintenance therapy (i.e. bevacizumab, PARP inhibitor) Cohort 1 and Cohort 3: No prior use of PARP inhibitor. Cohort 2: Prior use of PARP inhibitor. Cohort 3: No prior use of PARP inhibitor. Secondary cytoreductive surgery (SCR) when first recurrence Cohort 1 and Cohort 2: Never received SCR Cohort 2: Never received SCR Cohort 3: Received SCR Assessed by the experienced surgeons, complete resection of all recurrent disease is possible. Single or localized lesions identified by CT, or MRI, or positron emission tomography/computed tomography (PET/CT). PI and Co-PI reach consensus if extensive lesions or carcinomatosis. It can be included if single lesion outside the peritoneal cavity can be resected. No more than 3 disease lesions by central-reviewed PET/CT imaging if the participated center has never participated in any surgical trials on ovarian cancer before. Patients who have given their signed and written informed consent and their consent. Exclusion Criteria: Patients with borderline tumors as well as non-epithelial tumors. Patients for interval-debulking, or for second- or third-look surgery, or palliative surgery planned. Impossible to assess the resectability. Radiological signs suggesting complete resection is impossible. Patients who have received more than two previous regimen of chemotherapy (maintenance is not considered a third regimen). Third relapse or more. Patients with second or other malignancies who have been treated by surgery, if the treatment might interfere with the treatment of relapsed ovarian cancer or if major impact on prognosis is expected. Progression during chemotherapy or recurrence within 6 months after second-line platinum-based therapy Any contradiction not allowing surgery and/or chemotherapy and/or or Niraparib Accompanied by hypoxia serious chronic obstructive pulmonary disease Uncontrolled hypertension, cerebrovascular accident/ Stroke, myocardial infarct, unstable angina, untreated thrombosis, chronic congestive heart failure, or serious arrhythmia in need of medicine. Severe hepatitis, history of liver disease, nephrotic syndrome, renal insufficiency Active ulcer history, abdominal wall fistula, perforation of gastrointestinal tract, or Intra-abdominal abscess, or simultaneously apply treatment/prevent ulcers therapy. Uncontrolled diabetes Uncontrolled epilepsy need long-term antiepileptic treatment. Any medication induced considerable risk of surgery, e.g. estimated bleeding due to oral anticoagulating agents. ≥3 grade anemia, neutropenia or thrombocytopenia due to chemotherapy, and lasted for more than 4 weeks Patients with a known hypersensitivity to Niraparib or any of the excipients of the product.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized umbrella clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery<br>Intervention: Procedure: Maximum effort cytoreductive surgery combined with Niraparib maintenance Drug: Platinum-based chemotherapy and Niraparib | Procedure: Surgery<br>* Tumor debulking surgery (surgery in recurrent ovarian disease)<br>* Other names: secondary cytoreduction;Drug: carboplatin/taxane, carboplatin/gemcitabine, cisplatin/gemcitabine, liposome doxorubicin/carboplatin...<br>* Salvage chemotherapy<br>* Other names: third-line therapy;Drug: Niraparib<br>* Niraparib maintenance therapy<br>* Other names: maintenance therapy;|
| Active Comparator: No surgery<br>Intervention: Drug: Platinum-based chemotherapy and Niraparib | Drug: carboplatin/taxane, carboplatin/gemcitabine, cisplatin/gemcitabine, liposome doxorubicin/carboplatin...<br>* Salvage chemotherapy<br>* Other names: third-line therapy;Drug: Niraparib<br>* Niraparib maintenance therapy<br>* Other names: maintenance therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-month disease non-progression rate | 12-month non-progression rate | up to 12 months after last patient randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | from date of randomization until the date of 3rd relapse/progression or death (whatever occurs first) | Up to 24 months after last patient randomized | 
| Treatment free survival | It is the area between Kaplan-Meier curves for two time-to-event end points: 1) time to protocol chemotherapy cessation and 2) time to first subsequent anticancer therapy initiation or death, whichever occurred first. | Up to 24 months after last patient randomized | 
| Overall survival | from date of randomization until the date of death from any cause | Approximately up to 24 months after last patient randomized | 
| 30-day post-operative complications | surgical complications grading criteria will be adopted for evaluating the perioperative complications | From the operation until after 30 days | 
| Quality of life assessment | the European Organization for Research and Treatment (EORTC) core quality of life questionnaire (QLQ-C30, version 3.0) The total score (range from 0 to 1,000) | baseline; 6 and 12 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reurrent Ovarian Cancer, Secondary Cytoreductive Surgery, Chemotherapy, Niraparib maintenance