Study of Propranolol in Newly Diagnosed Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy
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|ClinicalTrials.gov Identifier: NCT01847001|
Recruitment Status : Active, not recruiting
First Posted : May 6, 2013
Last Update Posted : April 10, 2019
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:
- Determine the effect of propranolol plus chemotherapy on breast cancer cells as well as the growth of blood vessels surrounding breast cancer cells.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Malignant Neoplasm Breast Cancer||Drug: Propranolol Other: DOT imaging Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Trastuzumab Drug: Pertuzumab Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Surgery Drug: Premedication Drug: Anti-nausea therapy Drug: Pegfilgrastim||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of the Beta-blocker Propranolol Alone and With Chemotherapy in Patients Receiving Neoadjuvant Treatment for Newly Diagnosed Breast Cancer|
|Study Start Date :||October 2012|
|Actual Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2019|
Experimental: Propranolol + Neoadjuvant Chemotherapy
Subjects will receive 2 types of chemotherapy regimens plus propranolol treatment.
After you complete all chemotherapy plus propranolol treatment, you will then have surgery to remove the breast tumor.
DOT imaging will be done at 4 additional time points, including beo.
Propranolol starting dose is 20mg b.i.d.; propranolol dose is up-titrated to 40mg b.i.d. to 80 mg daily with chemotherapy depending on tolerability. Tolerability is assessed every 2 weeks.
Other: DOT imaging
(Non-experimental) During the baseline visit, you will undergo DOT evaluation of your tumor for determination of blood, fat, and water content in the affected and unaffected breast. DOT readings will be obtained at 4 additional time points: after paclitaxel week #3, before AC week #1, before AC week #3, and prior to surgery.
Other Name: Breast imaging - Diffuse Optical Tomography (DOT)
(Non-experimental) given as a one-hour intravenous infusion (IV) every week for a total of 12 weeks; the first dose of paclitaxel may be given over 90 minutes, per the discretion of your treating doctor. The dose will be given in 80 mg/m2 based on individual body surface area (BSA). This drug is given through a vein in the arm or a catheter (eg. Infusaport, Portacath).
Other Name: Abraxane
(Non-experimental) In the event paclitaxel is not available due to manufacturing and supply shortages, nab-paclitaxel will be substituted for paclitaxel. The dose is 100 mg/m2 IV infusion over 30 minutes weekly (or institutional standard). No premedications are given with nab-paclitaxel.
Other Name: Abraxane
(Non-experimental) (only if HER2-positive): Trastuzumab is given as an IV infusion initially over 90 minutes for the first dose, then 30-60 minutes every 3 weeks in subsequent doses if well tolerated. To be given every 3 weeks with paclitaxel/propranolol.
Other Name: Herceptin
(Non-experimental) (only if HER2-positive): Pertuzumab is given as an IV infusion over 60 minutes on the first dose, then 30-60 minutes every 3 weeks if well tolerated. To be given every 3 weeks with paclitaxel/propranolol.
Other Name: Perjeta
(Non-experimental) Doxorubicin will be given as a 510 minute intravenous infusion (IV) in a dose of 60 mg/m2; cyclophosphamide will be given as a 3060 minutes intravenous infusion (IV) in a dose of 600 mg/m2 based on BSA. This chemotherapy regimen will be given every 2 weeks for total of 8 weeks or 2 months.
Other Name: Adriamycin
(Non-experimental) Doxorubicin 60 mg/m2 IV over 5-10 minutes, Cyclophosphamide 600 mg/m2 IV infusion over 30-60 minutes. The first cycle should be initiated with 3 weeks after the last paclitaxel and/or trastuzumab/pertuzumab dose.
Other Name: AC
After you complete all chemotherapy plus propranolol treatment, you will then have surgery to remove the breast tumor if your doctor feels that it is medically appropriate (if you have had a good response to the treatment) - lumpectomy/mastectomy.
Other Name: No other name
As premedication to prevent some of the side effects associated with paclitaxel, you will also receive dexamethasone (Decadron) in a dose of 10 mg, diphenhydramine (Benadryl) in doses of 2550 mg, and an H2 blocker (eg. ranitidine 50 mg or equivalent) 3060 minutes before each paclitaxel infusion. If no hypersensitivity reactions are experienced, dexamethasone may be reduced in increments of 2 mg per week per dose (until a minimum of 2 mg has been reached).
Other Name: No other name
Drug: Anti-nausea therapy
In addition to doxorubicin, you will receive an anti-nausea therapy and dexamethasone about 3060 minutes before AC chemotherapy.
Other Name: No other name
When you receive the AC chemotherapy, you will also receive treatment with a drug called pegfilgrastim (Neulasta). Neulasta is a commercially available drug. It stimulates the production of white blood cells and reduces the likelihood of developing a low white blood cell count and fever after chemotherapy. It will be given as an injection under the skin on the day after each chemotherapy treatment (day 2).
Other Name: Neulasta
- Percentage of patients compliant with taking > 80% take the drug while on chemotherapy. [ Time Frame: Approximately 6 months ]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.
- Number of Patients with Adverse Events [ Time Frame: Approximately 6 months ]To assess the safety and tolerability of neoadjuvant propranolol in combination with chemotherapy as defined by Common Toxicity Criteria for Adverse Effects v.4.0
- Change in DOT-derived parameter (deoxyhemoglobin) [ Time Frame: Approximately 6 months ]Modulation of DOT markers, such as deoxyhemoglobin, at 5 time-points will be evaluated: a) prior to propranolol and taxane therapy; b) before starting taxane week #3; c) before starting adriamycin/Cytoxan (AC) cycle #1; d) before starting AC cycle #2; and e) before surgery.
- Change in tumor proliferation (ki-67) [ Time Frame: Approximately 6 months ]To evaluate reduction in tumor ki-67.
- Change in tumor density [ Time Frame: Approximately 6 months ]To evaluate the changes in blood or tumor based angiogenic markers, such as tumor microvessel density, seen with propranolol plus chemotherapy.
- Changes in stress level (score) [ Time Frame: Approximately 6 months ]To explore whether acute stress levels, as measured by responses to the Questionnaire on Stress in Cancer Patients - revised version (QSC-R23), associate propranolol biomarker changes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01847001
|United States, New York|
|Columbia University Irving Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Kevin M. Kalinsky, MD, MS||Columbia University|