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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Multicenter Randomized Study to Compare Neoadjuvant FDC With Melatonin or Metformin Versus FDC Alone in The Therapy of Locally Advanced Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: metformin
* Drug: Fluoruracil
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: melatonin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: FDC x 6 cycles with metformin<br>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 | Drug: metformin<br> <br> * Other names: siofor 850;Drug: Fluoruracil<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriablastin;Drug: Cyclophosphamide<br> <br> * Other names: endoxan;|
| Experimental: FDC x 6 cycles with melatonin<br>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 | Drug: Fluoruracil<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriablastin;Drug: Cyclophosphamide<br> <br> * Other names: endoxan;Drug: melatonin<br> <br> * Other names: melaxen;|
| Active Comparator: FDC x 6 cycles<br>32 patients will receive 5 - Fluoruracil 500 mg/m^2, doxorubicin 50 mg/m^2, cyclophosphamide 500 mg/m^2 once every 21 days | Drug: Fluoruracil<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriablastin;Drug: Cyclophosphamide<br> <br> * Other names: endoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Response will evaluate by RECIST criteria | 6 months after FPFV | 
| Pathomorphological response | Pathomorphological response will assess after surgery by Miller and Payne Scale | 6 months after FPFV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events incidence | Incidence of AE classified using NCI Common Terminology Criteria for AE v4 | 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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Melatonin, metformin, chemotherapy