Clinical trial NCT02596867: Neoadjuvant Propanolol in Breast Cancer
Official title: Pilot "Window of Opportunity" Neoadjuvant Study of Propranolol in Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: B adrenergic pathway
B Blocker
Lead sponsor: Texas Tech University Health Sciences Center, El Paso
Sponsor class: OTHER
First posted: 2015-11-04
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: * 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67.
timeFrame: 3 weeks
Secondary outcomes:
measure: Assess the Safety, Toxicity and Adherence to Propranolol.
timeFrame: 3 weeks
Other outcomes:
Locations:
city: El Paso
country: United States
facility: Texas Tech University HSC
state: Texas
Study officials:
affiliation: Texas Tech University Health Sciences Center, El Paso
name: Zeina Nahleh, MD
role: PRINCIPAL_INVESTIGATOR
References: