Efficacy of Statin Addition to Neoadjuvant Chemotherapy Protocols for Breast Cancer

Study Overview
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Brief Summary
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Different modalities for breast cancer treatments have exhausting and distressing side effects and toxicities leading to decreased compliance. Thus, repurposing drugs with accepted safety profile and possible antitumor activity becomes an eminent constraint. Statins have been reported to have possible advantages as anticancer, and control of cancer progression. Moreover, they can sensitize cancer cells for radiotherapy. Therefore, the investigators aim to investigate the effect of (pitavastatin) added to conventional chemotherapy protocols for breast cancer patients.

Official Title
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Efficacy of Statin Addition to Neoadjuvant Chemotherapy Protocols for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pitavastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent before any study-specific procedures. Histologic confirmation of invasive breast cancer. Plans for the administration of neoadjuvant chemotherapy. Not currently pregnant during the study Exclusion Criteria: Severe gastrointestinal disorder Current use of statins or fibrates for any time during the 3 months before the study Proven hypersensitivity to statins Currently on medication for hypercholesterolemia Strong Cytochrome P450 3A4 (abbreviated CYP3A4) (e.g., clarithromycin, HIV protease inhibitors, and itraconazole), given potential interactions with statins Renal impairment with a creatinine > 1.4 mg/dl Hepatic impairment: Aspartate transaminase (AST)/(SGOT), Alanine Transaminase (ALT)/(SGPT) ≥ 2.5 x upper limit of the normal range (ULN), OR Total bilirubin ≥ 1.5 x ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN), OR Alkaline phosphatase > 2.5 x ULN Central nervous system (CNS) diseases and major psychiatric diseases or inability to comply with the protocol procedures Active infections Cardiac failure, class I-IV Current anticoagulant or antiplatelet aggregation therapy Current lactation

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pitavastatin group<br>For the intended neoadjuvant treatment period, participants will receive -in addition to standard chemotherapy protocol - Pitavastatin tablets 2 mg once daily. | Drug: Pitavastatin<br>* Pitavastatin 2 mg oral tablets daily will be given to the patients concomitantly with the intended chemotherapy protocol for the treatment period prior to surgery.<br>* Other names: HMG CoA reductase inhibitor  Lipovastatin;|
| Placebo Comparator: Placebo group<br>For the intended neoadjuvant treatment period, participants will receive -in addition to standard chemotherapy protocol - Placebo tablets matching pitavastatin orally once daily. | Drug: placebo<br>* patients in this group will receive placebo tablets concomitantly with the intended chemotherapy for the treatment period prior to surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical response rate | Response to preoperative therapy as per ultrasonographic tumor size assessment. A responder will have > 50% decrease in the size of the primary tumor without appearance of new lesions. | 6 months | 
| Relative reduction of Ki67 in tumor samples | It will be described as average pre-post differences in percent positive cells with 95% Wilson confidence intervals. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in Cyclin D1 (candidate marker associated with breast tumor proliferation) |  | Baseline up to 6 months | 
| The change in Cleaved caspase-3 (CC3) (candidate marker associated with tumor apoptosis) |  | Baseline up to 6 months |