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

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)).

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Procedure: chemotherapy/surgery

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Igor Berlev; Phone Number: +79219612777; Email: iberlev@gmail.com
• Study Contact Backup: Name: Tatyana Gorodnova; Phone Number: +79213058218; Email: t.gorodnova@mail.ru

Study Locations

• Russian Federation
  • Pesochny-2, St.-Petersburg
    • St.-Petersburg, Pesochny-2, St.-Petersburg, Russian Federation, 197758
      • Recruiting
      • NMRC of Oncology named after N.N.Petrov of MoH of Russia
      • Contact: Gorodnova Tatyana; Phone Number: 8-921-305-82-18; Email: t.gorodnova@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

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: Mitomycin C and cisplatin regimen; mitomycin C at 10 mg/m2 and cisplatin at 100 mg/m2	Procedure: chemotherapy/surgery; NEO chemotherapy/interval debulking surgery/AD chemotherapy
Active Comparator: Paclitaxel and carboplatin regimen; paclitaxel at 175 mg/m2 and carboplatin AUC5-6	Procedure: chemotherapy/surgery; NEO chemotherapy/interval debulking surgery/AD chemotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: N.N. Petrov National Medical Research Center of Oncology
• Investigators: Study Chair: Igor Berlev, National Medical Research Centre of Oncology named after N.N. Petrov

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Ovarian cancer; Neoadjuvant chemotherapy; Mitomycin C
• 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; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: OvCa-NeoMP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No