Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer

Study Overview
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Brief Summary
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This study was designed to assess the safety and efficacy of neoadjuvant therapy with mitomycin C plus cisplatin (MP) in BRCA1-mutated ovarian cancer versus standard regimen (paclitaxel plus carboplatin (TP)).

Detailed Description
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The trial includes two arms, one of which is experimental arm with MP regimen chemotherapy that is compared with other arm with the standard TC regimen chemotherapy. To participate in this study, patients must have histologically confirmed epithelial ovarian carcinoma (ОС) or fallopian tubes carcinoma and FIGO stage IIB, IIC, III, or IV disease and BRCA1/BRCA2 germline mutation. All OC patients before the treatment start are subjected to the testing for BRCA1/BRCA2 mutations cases that are examined by the next-generation sequencing. All BRCA1/2 mutation carriers, who could not be treated by primary debulking surgery owing to extensive tumor spread, are given neoadjuvant chemotherapy. OC patients are randomly assigned to receive the TP regimen (paclitaxel at175 mg/m2 and carboplatin AUC5-6) or the MP regimen (mitomycin C at 10 mg/m2 and cisplatin at 100 mg/m2). After 3-4 cycles of neoadjuvant chemotherapy, a formal assessment is made and patients are categorized according to the RECIST 1.1 standard. The patients who show partial clinical response or complete clinical response has to be undergoing interval debulking surgery. The patients who show stabilization of the process should continue chemotherapy for up to 6 cycles, followed by an assessment of the treatment (it is possible to continue up to 12 cycles) and a decision on whether to perform interval debulking surgery. Patients categorized as progressed clinically has to finish the protocol treatment and are allowed to receive any secondary treatment at the investigators' discretion. For those patients undergoing interval debulking surgery has to receive further regimens (up to 6 cycles of protocol treatment) without changing chemotherapy regimen. After six cycles of protocol treatment, the patients had to be categorized with regard to their final response status with the use of clinical/radiologic assessment. Patients not showing disease progression at this point could cease all cytotoxic therapy or can receive three additional cycles of protocol treatment. While on protocol therapy, patients underwent the following procedures: symptom recording and physical examination every 3 weeks, complete blood cell counts weekly for the first two cycles and every 3 weeks thereafter, and laboratory tests of blood and CA 125 measurements on day 1 of each cycle. Radiologic investigations to document the status of all measurable lesions noted at baseline had to be repeated after three, six, and nine cycles of chemotherapy. Once patients were off the protocol therapy, they were monitored for assessment of disease status every 3 months for 2 years and every 6 months thereafter. Monitoring comprised clinical examination and CA 125 estimation; routine computed tomography scans were not required but were requested if the CA 125 level rose and/or symptoms developed.

Official Title
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Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Procedure: chemotherapy/surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed epithelial ovarian carcinoma or fallopian tubes carcinoma FIGO stage IIB, IIC, III, or IV disease BRCA1/BRCA2 germline mutation Exclusion Criteria: WHO performance status >3 FIGO early stage wt BRCA status cytological verification

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mitomycin C and cisplatin regimen<br>mitomycin C at 10 mg/m2 and cisplatin at 100 mg/m2 | Procedure: chemotherapy/surgery<br>* NEO chemotherapy/interval debulking surgery/AD chemotherapy<br>|
| Active Comparator: Paclitaxel and carboplatin regimen<br>paclitaxel at 175 mg/m2 and carboplatin AUC5-6 | Procedure: chemotherapy/surgery<br>* NEO chemotherapy/interval debulking surgery/AD chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | To assess the objective response rate (OR) by RECIST v1.1 2. Pathologic response | 4 months after FPFV | 
| Pathomorphological response | Pathomorphological response will assess after surgery by Bohm scale | 4 months after FPFV | 
| Progression Free Survival | As per RECIST v1.1. progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events incidence | is defined as the interval between the date last chemotherapy cycle and the date of progression of the disease or death or start of a new therapy without evidence of progression, whichever occurred first | Until 30 days after last patient treatment visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, Neoadjuvant chemotherapy, Mitomycin C