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Locally Advanced Malignant NeoplasmPhase 2NCT01847001

Study of Propranolol in Newly Diagnosed Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

A Phase 2 study testing Propranolol, DOT imaging and Paclitaxel in people with Locally Advanced Malignant Neoplasm and Breast Cancer, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Propranolol, DOT imaging and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Oct 2012to 16 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Columbia University Irving Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: A 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.

Read the detailed description

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.

Being tested
Propranolol, DOT imaging, Paclitaxel, Nab-paclitaxel, Trastuzumab
Keywords
Breast Cancer, Neoadjuvant, Experimental, Biomarker, Breast imaging
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PropranololDrug

    Also called Inderal, Inderal LA ®, InnoPran XL ®

    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.

  • DOT imagingOther

    Also called Breast imaging - Diffuse Optical Tomography (DOT)

    (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.

  • PaclitaxelDrug

    Also called Abraxane

    (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).

  • Nab-paclitaxelDrug

    Also called 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.

  • TrastuzumabDrug

    Also called Herceptin

    (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.

  • PertuzumabDrug

    Also called Perjeta

    (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.

  • DoxorubicinDrug

    Also called Adriamycin

    (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.

  • CyclophosphamideDrug

    Also called AC

    (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.

  • SurgeryProcedure or surgery

    Also called No other name

    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.

  • PremedicationDrug

    Also called 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).

  • Anti-nausea therapyDrug

    Also called No other name

    In addition to doxorubicin, you will receive an anti-nausea therapy and dexamethasone about 3060 minutes before AC chemotherapy.

  • PegfilgrastimDrug

    Also called Neulasta

    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).

Study groups in NCT01847001
Study groupRoleWhat they receive
Propranolol + Neoadjuvant ChemotherapyExperimentalSubjects will receive 2 types of chemotherapy regimens plus propranolol treatment. * Regimen I, involves paclitaxel (may be substituted with nab-paclitaxel; maybe given with premedication), and * Regimen II involves doxorubicin (maybe given with anti-nausea therapy) and cyclophosphamide (maybe given with Pegfilgrastim). * If your tumor is HER2 positive, you will also receive trastuzumab and pertuzumab. 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Adherence to Propranolol

    Propranolol adherence was documented biweekly by pill counts and drug diary checks.

    Measured: Approximately 6 months

  2. Total Number of Participants Who Reached The Target Propranolol Dosing

    The target Propranolol dosing was 80mg ER daily.

    Measured: Approximately 6 months

Secondary outcomes (1)
  1. Number of Patients With Pathologic Complete Response

    Response was confirmed with pathology.

    Measured: Approximately 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2013 (estimated)
  2. Study startOct 2012
  3. Primary completion31 Dec 2018
  4. Study completion16 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01847001
Sponsor's protocol ID
AAAI9158
Other IDs
UL1TR000040
Status last verified
Aug 2021
First submitted
23 Apr 2013
Last updated
10 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Propranolol, DOT imaging and Paclitaxel in people with Locally Advanced Malignant Neoplasm and Breast Cancer, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Adherence to Propranolol (time frame: Approximately 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2021.

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