Neoadjuvant Toremifene With Melatonin or Metformin in 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 toremifene in the treatment of locally advanced breast cancer. Third of patients will receive toremifene, other third will receive combination of melatonin and toremifene and other patients will receive combination of metformin and toremifene.

Detailed Description
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The management of locally advanced breast cancer is complicated issue. Neoadjuvant treatment is often needed to downstage locally advanced ER positive BC tumors prior to surgery. However, many patients do not achieved objective response on 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 anti - estrogen treatment may increase objective response. But, this data is still controversial. We hypothesizes that the combinations of melatonin and metformin with conventional anti - estrogen such as toremifene could be more effective than toremifene alone in terms of response rate.

Official Title
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Phase II Multicenter Randomized Study to Compare Neoadjuvant Toremifene With Melatonin or Metformin Versus Toremifene in the Therapy of Locally Advanced Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: metformin
* Drug: Melatonin
* Drug: Toremifene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18. Obtained Inform Concent. Morphologically confirmed breast cancer stage IIB, IIIA, IIIB, IIIC ER positive. 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. Stage IV 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 investigators 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: Toremifene and metformin<br>Toremifene 60 mg daily with metformin 850 mg BID | Drug: metformin<br> <br> * Other names: siofor 850;Drug: Toremifene<br> <br> * Other names: farestone;|
| Experimental: Toremifene and melatonin<br>Toremifene 60 mg daily with melatonin 3 mg before sleep daily | Drug: Melatonin<br> <br> * Other names: melaxen;Drug: Toremifene<br> <br> * Other names: farestone;|
| Active Comparator: Toremifene<br>Toremifene 60 mg daily | Drug: Toremifene<br> <br> * Other names: farestone;|

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 | 4 months after FPFV | 
| Pathomorphological response | Pathomorphological response will assess after surgery by Miller and Payne Scale | 4 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, toremifene