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A Phase II Study of the Beta-blocker Propranolol Alone and With Chemotherapy in Patients Receiving Neoadjuvant Treatment for Newly Diagnosed Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Locally Advanced Breast Cancer

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Trial Information

A Phase II Study of the Beta-blocker Propranolol Alone and With Chemotherapy in Patients Receiving Neoadjuvant Treatment for Newly Diagnosed Breast Cancer

While a number of therapeutic options exist for patients with breast cancer (BC), breast
tumor biology is differs across tumors and not all BCs respond to treatment. Identifying a
marker predicting response could spare non-responders unnecessary side effects, cost, and
time. A recent example in BC is bevacizumab, an expensive anti-angiogenic monoclonal
antibody, for which the FDA revoked approval for patients with metastatic BC. While this
targeted therapy may benefit some patients, no appropriate predictive marker has been
identified in the drug development process. An ideal biologic marker would be easy to
perform, reliable, low-cost and non-invasive. A limitation of assessing tumor-based markers
in metastatic BC is the inability to procure tumor tissue at different treatment times. To
circumvent this issue, anti-cancer agents can be assessed pre-operatively, where women with
newly diagnosed BC receive a study drug, alone or with chemotherapy, between diagnostic
breast biopsy and surgical resection. In addition, tumor changes can be directly compared to
modulation of non-invasive markers, such as functional radiographs or blood, to identify a
non-invasive marker predicting tumor response.

The investigators are conducting a neoadjuvant single-institution trial with the
non-selective, inexpensive β -blocker propranolol alone and with chemotherapy in locally
advanced BC. β-blockade regulates angiogenesis in primary breast tumors. In these trials,
the investigators plan to evaluate treatment-related microvascular response via changes in
breast Diffuse Optical Tomography (DOT), a non-invasive, fast, safe, and inexpensive breast
imaging tool. As the optical property contrast from endogenous chromophores (oxyhemoglobin,
deoxyhemoglobin, water, and lipid) provides information on tissue vascularity, it can
monitor response to anti-angiogenic agents. DOT changes occur as early as 1 week after
starting pre-operative therapy. The dynamic DOT system incorporated in these trials is
unique to Columbia University Medical Center (CUMC), as it has been designed by Columbia
biomedical engineers. CUMC's laboratory collaborators have measured this DOT system with
anti-angiogenesis agents in animal models, demonstrating the translational nature of this
project. While non-dynamic DOT has been assessed in other neoadjuvant trials with small
cohorts receiving heterogeneous chemotherapy agents, none have evaluated DOT response to
anti-angiogenic agents.

Inclusion Criteria:

- English or Spanish speaking women age ≥18

- Bra cup no larger than DD, given that DOT cannot measure breast size larger than DD

- Heart Rate > 60 bpm

- Systolic Blood Pressure > 100 mm/Hg

- Deemed eligible to receive neoadjuvant chemotherapy with 12 cycles of weekly taxane
therapy (paclitaxel 80mg/m2 or abraxane 100 mg/m2 if there is a shortage of
paclitaxel) followed by 4 cycles of adriamycin (60mg/m2) and cyclophosphamide (600
mg/m2) given every 2 weeks with growth-factor support.

- Echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) with ejection
fraction > 50%.

- Patients with hormone receptor +/- and human epidermal growth factor receptor 2
protein (HER2) +/- breast cancer are eligible

- If a patient has HER2-positive breast cancer, Herceptin will be given along with
taxane therapy

- Any stage invasive breast cancer provided the primary breast tumor size is ≥ 1 cm

- Agree to participate in research blood collection at 4 different time periods (20 ml
= 4 teaspoons)

- Agree to the evaluation of already collected core biopsy, as well as surgical
resection tissue, for predictive biomarkers. The biopsy prior to Taxol #1 is

Exclusion Criteria:

- Patients failing to meet the inclusion criteria

- Corrected QT interval (QTc) prolongation as defined by > 470 milliseconds on
electrocardiogram (ECG)

- First degree AV block on ECG in which PR interval lengthened > 200 milliseconds;
Second Degree; or Third Degree

- On beta-blocker treatment. If discontinued, patients must have been off
beta-blockers for at least 3 months.

- History of asthma, given concern for β-blockade in this population

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

Percentage of patients who are compliant with taking > 80% take the drug while on chemotherapy.

Outcome Description:

Feasibility will be assessed: The combination will be deemed feasible if at least 75% of patients (15 patients) are compliant with taking > 80% take the drug on a daily basis as prescribed (nonadherence/medication possession ratio < 20%). This rate is higher than the 52% compliance rate, defined by dose reduction or interruption, in other series with oral therapies in the neoadjuvant setting.

Outcome Time Frame:

Approximately 6 months

Safety Issue:


Principal Investigator

Kevin M. Kalinsky, MD, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University


United States: Institutional Review Board

Study ID:




Start Date:

October 2012

Completion Date:

October 2014

Related Keywords:

  • Locally Advanced Breast Cancer
  • Breast Cancer
  • Neoadjuvant
  • Experimental
  • Biomarker
  • Breast imaging
  • Breast Neoplasms



Columbia University Medical Center New York, New York  10032