Breast Cancer
Conditions
Keywords
B adrenergic pathway, B Blocker
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.
Interventions
DRUGpropanolol
Participants will take 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed
Sponsors
Texas Tech University Health Sciences Center, El Paso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Recruitment details
Prospective - two breast cancer patients enrolled over 6 months perios from clinic .
Participants by arm
| Arm | Count |
|---|---|
| Open Label Single Arm, Drug Propanolol 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 | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Open Label Single Arm, Drug Propanolol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor response by Ki 67 | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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
Time frame: 3 weeks
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label Single Arm, Drug Propanolol | Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67. | Stage I Patient 1 | 23 % mean difference of Ki67 |
| Open Label Single Arm, Drug Propanolol | Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67. | Stage III Patient 2 | 66 % mean difference of Ki67 |
Secondary
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)
Time frame: 3 weeks
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Single Arm, Drug Propanolol | Assess the Safety, Toxicity and Adherence to Propranolol. | 0 Participants |