Study of Propranolol in Newly Diagnosed Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/31/2019 |
| Start Date: | October 2012 |
| End Date: | December 2019 |
A Phase II Study of the Beta-blocker Propranolol Alone and With Chemotherapy in Patients Receiving Neoadjuvant Treatment for Newly Diagnosed Breast Cancer
This study is being conducted in patients with newly diagnosed breast cancer that will be
undergoing chemotherapy prior to surgery - neoadjuvant chemotherapy. The study involves
treatment with standard chemotherapy and a commonly used, FDA-approved, blood pressure drug
called propranolol (Inderal). The purposes of this study are to:
1. Determine the effect of propranolol plus chemotherapy on breast cancer cells as well as
the growth of blood vessels surrounding breast cancer cells.
2. Determine the side effect profile of propranolol and chemotherapy in patients with
breast cancer receiving neoadjuvant chemotherapy.
This research is being done because previous laboratory work has shown that propranolol may
decrease the ability for the blood vessels around breast cancer cells to grow, which may be
important in helping cancer cells grow. It also may reduce the likelihood for breast cancer
cells to spread. If changes are seen in the breast cancer cells and surrounding blood vessels
in this study, we will pan to evaluate whether propranolol decreases the likelihood of breast
cancer from recurring in future, later studies. All chemotherapy regimens used in this study
have been the standard of care for many years; however, the use of propranolol is being
researched along with the chemotherapy regimens.
undergoing chemotherapy prior to surgery - neoadjuvant chemotherapy. The study involves
treatment with standard chemotherapy and a commonly used, FDA-approved, blood pressure drug
called propranolol (Inderal). The purposes of this study are to:
1. Determine the effect of propranolol plus chemotherapy on breast cancer cells as well as
the growth of blood vessels surrounding breast cancer cells.
2. Determine the side effect profile of propranolol and chemotherapy in patients with
breast cancer receiving neoadjuvant chemotherapy.
This research is being done because previous laboratory work has shown that propranolol may
decrease the ability for the blood vessels around breast cancer cells to grow, which may be
important in helping cancer cells grow. It also may reduce the likelihood for breast cancer
cells to spread. If changes are seen in the breast cancer cells and surrounding blood vessels
in this study, we will pan to evaluate whether propranolol decreases the likelihood of breast
cancer from recurring in future, later studies. All chemotherapy regimens used in this study
have been the standard of care for many years; however, the use of propranolol is being
researched along with the chemotherapy regimens.
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 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.
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 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
- 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 and Perjeta 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 optional.
Exclusion Criteria:
- Patients failing to meet the inclusion criteria
- Corrected QT interval (QTc) prolongation as defined by > 470 milliseconds on
electrocardiogram (ECG)
- First-degree Atrioventricular (AV) block on ECG in which P-R 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
We found this trial at
1
site
630 W 168th St
New York, New York
New York, New York
212-305-2862
Principal Investigator: Kevin M. Kalinsky, MD, MS
Phone: 212-305-5528
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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