Neoadjuvant Propanolol in Breast Cancer

Study Overview
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Brief Summary
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This trial is a Phase II study using the window-of-opportunity design in which the treatment-free window between breast cancer diagnosis and surgical tumor resection is used to study the biological effects of the beta blocker propranolol .

Detailed Description
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Patients will be recruited from the Garbar Breast Care Center and University Medical Center following diagnosis of invasive breast cancer by breast biopsy. The sympatholytic nonselective beta blocker propranolol will be administered to all participants in a non-randomized manner at an equal dose of 1.5 mg/kg/day. Following surgical resection of the tumor , the primary endpoint of this study is quantified by comparing the proliferative index of the tumor before propranolol administration (quantified using the initial tumor biopsy) and after 3 weeks of propranolol (quantified using the surgically resected tumor). Additional molecular analyses and evaluation of safety and toxicity will also be performed to better understand the effects of this treatment on breast cancers and patient adherence to the drug.

Official Title
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Pilot Window of Opportunity Neoadjuvant Study of Propranolol in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: propanolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18- 65 diagnosis of stage I-III breast cancer , confirmed by a core biopsy Planning to undergo definitive surgery including mastectomy or breast conserving surgery Systolic blood pressure must be >100 mmHg but no more than 140 mmHg and/or diastolic > 60 mmHg and no more than 95 mmHg. normal baseline EKG Exclusion criteria: Pregnancy; potential subjects of female bearing age will have to complete a pregnancy test during screening to ensure that they are not pregnant. Potential patients who are post-menopausal must have confirmed one year without menstrual cycle. Free of major medical illnesses including: Uncontrolled Diabetes (HbA1c of ≤ 8 if previously tested) Uncontrolled hypertension: BP >systolic 140/ diastolic > 95 Cardiac diseases (history of cardiac valve disease, coronary artery disease, congestive heart failure, A-V block, peripheral vascular disease, any cardiac arrhythmia/bradycardia) with the exception of the diagnosed cancer. Histories of asthma, bronchospastic disease, or obstructive pulmonary disease Previously diagnosed thyrotoxicosis Severe allergic reactions to medications which are included in the beta blocker family Previously or currently treated with a beta adrenergic receptor antagonist Patients with locally advanced or inflammatory breast cancer not amenable to surgical resection Patients taking any of the following medications will be excluded: Drugs that are categorized as digitalis glycosides, beta-blockers and calcium channel blockers, ACE inhibitors and alpha blockers Amiodarone Cimetidine Ciprofloxacin Delavudin Dobutamine Ethanol Fluconazole Fluoxetine Fluvoxamine Haloperidol Imipramine Isoniazid Isoproterenol Luvoxamine Paroxetine Phenytoin Phenobarbital. Propafenone. Quinidine Reserpine Rifampin Ritonavir Rizatriptan. Tenioposide Theophylline Thyroxine Tolbutamide. Warfarin Zileuton Zolmitriptan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: open label single arm, drug propanolol<br>all subjects will receive the experimental drug | Drug: propanolol<br>* Participants will take 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67. | to evaluate effect of beta adrenergic blockades on breast cancer at by Ki67 percentage change- we are looking at at least 10% mean change in the tumor proliferative index following propranolol treatment | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Safety, Toxicity and Adherence to Propranolol. | Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.(Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4) | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B adrenergic pathway, B Blocker