Neoadjuvant FDC With Melatonin or Metformin for Locally Advanced Breast Cancer.

Phase 2

• Conditions: Breast Cancer
• Interventions: Drug: metformin; Drug: Fluoruracil; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: melatonin

• Registration Number: NCT02506777
• Lead Sponsor: N.N. Petrov National Medical Research Center of Oncology

Brief Summary

This study evaluates the addition melatonin and metformin to conventional chemotherapy FDC (Fluoruracil, Doxorubicin, cyclophosphamide) in the treatment of locally advanced breast cancer. Third of patients will receive FDCх6 cycles, other third will receive combination of melatonin and FDCх6 cycles and other patients will receive combination of metformin and FDCх6 cycles.

Detailed Description

The treatment of locally advanced breast cancer is a complicated issue. For neoadjuvant treatment is often needed to downstage locally advanced BC tumors prior to surgery, however many patients do not achieved objective response during treatment. The ability of melatonin and metformin to decrease side effects of chemotherapy had been investigated, moreover several studies confirm, that this drugs in combination with conventional treatment may increase objective response. But, this data is still controversial. We hypothesized that combinations of melatonin and conventional chemotherapy regimen such as FDC could be more effective than FDC alone in terms of response rate.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-07-21
• Study First Submitted QC: 2015-07-22
• Study First Posted: 2015-07-23
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-02
• Last Update Posted: 2019-09-04
• Primary Completion: 2020-08
• Study Completion: 2020-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 96

Inclusion Criteria

• Age >18. Obtained Inform Consent Morphologically confirmed breast cancer stage IIB, IIIA,IIIB,IIIC. ( triple negative, luminal B) Eastern Collaborative Oncology Group Performance Status Scale 0 - 2. Expected survival >6 month Adequate liver and bone marrow function

Exclusion Criteria

• Systemic treatment for breast cancer IV stage disease Evidence of liver and bone marrow clinically meaningful disfunction Severe uncontrolled concomitant conditions and diseases Pregnancy or lactation Second malignancy Diabetes mellitus requiring drug therapy Any condition preventing study participation by investigator opinion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FDC x 6 cycles with metformin	Fluoruracil	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with metformin 850 mg BID
FDC x 6 cycles with melatonin	Fluoruracil	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with melatonin 3 mg before sleep daily
FDC x 6 cycles	Fluoruracil	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days
FDC x 6 cycles with metformin	metformin	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with metformin 850 mg BID
FDC x 6 cycles with metformin	Cyclophosphamide	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with metformin 850 mg BID
FDC x 6 cycles with metformin	Doxorubicin	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with metformin 850 mg BID
FDC x 6 cycles with melatonin	Doxorubicin	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with melatonin 3 mg before sleep daily
FDC x 6 cycles with melatonin	melatonin	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with melatonin 3 mg before sleep daily
FDC x 6 cycles with melatonin	Cyclophosphamide	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days with melatonin 3 mg before sleep daily
FDC x 6 cycles	Cyclophosphamide	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days
FDC x 6 cycles	Doxorubicin	32 patients will receive 5 - Fluoruracil 500 mg/m\^2, doxorubicin 50 mg/m\^2, cyclophosphamide 500 mg/m\^2 once every 21 days

Primary Outcome Measures

Name	Time	Method
Response rate	6 months after FPFV	Response will evaluate by RECIST criteria
Pathomorphological response	6 months after FPFV	Pathomorphological response will assess after surgery by Miller and Payne Scale

Secondary Outcome Measures

Name	Time	Method
Adverse events incidence	Until 30 days after last patient treatment visit	Incidence of AE classified using NCI Common Terminology Criteria for AE v4

Trial Locations

Locations (1)

N.N. Petrov Research Institute of Oncology Clinical Diagnostic Department; 🇷🇺 Saint - Petersburg, Russian Federation