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

NCT01847001 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AAAI9158UL1TR000040
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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). The purposes of this study are to:

1. 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. 2.Determine the side effect profile of propranolol and chemotherapy in patients with breast cancer receiving neoadjuvant chemotherapy.

Conditions

Locally Advanced Malignant Neoplasm; Breast Cancer

Keywords

Breast Cancer; Neoadjuvant; Experimental; Biomarker; Breast imaging

Outcome Measures

Primary Outcomes (2)

• Mean Adherence to Propranolol

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

  Approximately 6 months

• Total Number of Participants Who Reached The Target Propranolol Dosing

  The target Propranolol dosing was 80mg ER daily.

  Approximately 6 months

Secondary Outcomes (1)

• Number of Patients With Pathologic Complete Response

  Approximately 6 months

Study Arms (1)

Propranolol + Neoadjuvant Chemotherapy

EXPERIMENTAL

Subjects 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.

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

Interventions

Propranolol DRUG

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.

Also known as: Inderal, Inderal LA ®, InnoPran XL ®

Propranolol + Neoadjuvant Chemotherapy

DOT imaging OTHER

(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.

Also known as: Breast imaging - Diffuse Optical Tomography (DOT)

Propranolol + Neoadjuvant Chemotherapy

Paclitaxel DRUG

(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).

Also known as: Abraxane

Propranolol + Neoadjuvant Chemotherapy

Nab-paclitaxel DRUG

(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.

Also known as: Abraxane

Propranolol + Neoadjuvant Chemotherapy

Trastuzumab DRUG

(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.

Also known as: Herceptin

Propranolol + Neoadjuvant Chemotherapy

Pertuzumab DRUG

(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.

Also known as: Perjeta

Propranolol + Neoadjuvant Chemotherapy

Doxorubicin DRUG

(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.

Also known as: Adriamycin

Propranolol + Neoadjuvant Chemotherapy

Cyclophosphamide DRUG

(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.

Also known as: AC

Propranolol + Neoadjuvant Chemotherapy

Surgery PROCEDURE

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.

Also known as: No other name

Propranolol + Neoadjuvant Chemotherapy

Premedication DRUG

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).

Also known as: No other name

Propranolol + Neoadjuvant Chemotherapy

Anti-nausea therapy DRUG

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

Also known as: No other name

Propranolol + Neoadjuvant Chemotherapy

Pegfilgrastim DRUG

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).

Also known as: Neulasta

Propranolol + Neoadjuvant Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Propranolol; propranolol CR; Paclitaxel; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Trastuzumab; pertuzumab; Doxorubicin; Cyclophosphamide; Surgical Procedures, Operative; Premedication; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Kevin Kalinsky
• Organization: Columbia University Medical Center

cancerclinicaltrials@cumc.columbia.edu

212-305-1925

Study Officials

• Kevin M. Kalinsky, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: May 6, 2013
• Study Start: October 1, 2012
• Primary Completion: December 31, 2018
• Study Completion: October 16, 2019
• Last Updated: September 10, 2021
• Results First Posted: January 10, 2020

Record last verified: 2021-08

Locations

US (1)