NPBC: Neoadjuvant Propanolol in Breast Cancer

• Sponsor: Texas Tech University Health Sciences Center, El Paso (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02596867
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 20
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 .

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: propanolol	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot "Window of Opportunity" Neoadjuvant Study of Propranolol in Breast Cancer
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67. [3 weeks]

   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

Secondary Outcome Measures

1. Assess the Safety, Toxicity and Adherence to Propranolol. [3 weeks]

   Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.(Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texas Tech University HSC	El Paso	Texas	United States	79905

Sponsors and Collaborators

• Texas Tech University Health Sciences Center, El Paso

Investigators

• Principal Investigator: Zeina Nahleh, MD, Texas Tech University Health Sciences Center, El Paso

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 26, 2016

More Information

Publications

None provided.

• Responsible Party: Zeina Nahleh, Professor, Texas Tech University Health Sciences Center, El Paso
• ClinicalTrials.gov Identifier: NCT02596867
• Other Study ID Numbers: E15123
• First Posted: Nov 4, 2015
• Last Update Posted: Mar 1, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Zeina Nahleh, Professor, Texas Tech University Health Sciences Center, El Paso: B adrenergic pathway; B Blocker
• Additional relevant MeSH terms: Breast Neoplasms; Propranolol

Study Results

Participant Flow

Recruitment Details	Prospective - two breast cancer patients enrolled over 6 months perios from clinic .

Arm/Group Title	Open Label Single Arm, Drug Propanolol
Arm/Group Description	2 subjects enrolled and received the experimental drug propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed
Period Title: Overall Study
STARTED	2
2 Patients Prospectively Recruited	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Open Label Single Arm, Drug Propanolol
Arm/Group Description	2 subjects enrolled and received the experimental drug propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%
Tumor response by Ki 67 (Count of Participants)
Count of Participants [Participants]	2 100%

Outcome Measures

1. Primary Outcome

Title	Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67.
Description	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
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Two patients with breast cancer are included in this analysis. One patient was a stage I breast cancer and the second patient was a stage III breast cancer.

Arm/Group Title	Open Label Single Arm, Drug Propanolol
Arm/Group Description	We tested the efficacy of propranolol on two patients with breast cancer by recording % reduction of Ki67
Measure Participants	2
Stage I Patient 1	23
Stage III Patient 2	66

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Two patients with breast cancer are included in this analysis. One patient was a stage I breast cancer and the second patient was a stage III breast cancer, AEs were assessed during and after treatment

Arm/Group Title	Open Label Single Arm, Drug Propanolol
Arm/Group Description	2 subjects enrolled and received the experimental drug propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed Both patients reported no AEs due to treatment during treatment phase
Measure Participants	2
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	AEs were monitored during and at the end of treatment (a total of 3 weeks)
Adverse Event Reporting Description	Zero AEs were reported/observed during and at the end of treatment. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4
Arm/Group Title	Open Label Single Arm, Drug Propanolol
Arm/Group Description	all subjects will receive the experimental drug propanolol: Participants will take 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed
All Cause Mortality
	Open Label Single Arm, Drug Propanolol
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Open Label Single Arm, Drug Propanolol
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Open Label Single Arm, Drug Propanolol
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

slow accrual was noted , mostly due to scheduling of surgery

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.