Losartan in Prevention of Radiation-Induced Heart Failure

The Role of Losartan in the Prevention of Early Structural Changes Associated With Radiation-Induced Heart Failure

This study is being done to see if losartan affects the chances of developing radiation-induced heart failure in patients who are receiving radiation therapy as part of standard of care treatment for breast cancer.

The interventions involved in this study are:

• Losartan
• Radiation Therapy (standard of care)

Study Overview

• Status: Recruiting
• Conditions: Myocardial Fibrosis; Breast Cancer; Radiation-Induced Fibrosis
• Intervention / Treatment: Drug: Losartan; Radiation: Radiation Therapy

Detailed Description

This is a pilot study examining whether losartan prevents radiation therapy-induced myocardial fibrosis (thickening of the heart tissue), which can cause heart failure, in breast cancer patients receiving radiation therapy.

Losartan is an U.S. Food and Drug Administration (FDA) approved drug used to treat hypertension (high blood pressure) and heart failure. The U.S. Food and Drug Administration (FDA) has not approved losartan for use in the treatment of breast cancer.

The FDA has approved radiation therapy as a treatment option for breast cancer.

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits. It is expected participants will be on the study for 1 year.

It is expected that about 10 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Rachel Jimenez, MD; Phone Number: 617-726-8651; Email: RBJIMENEZ@PARTNERS.ORG

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital Cancer Center
      • Contact: Rachel Jimenez, MD; Phone Number: 617-726-8651; Email: RBJIMENEZ@PARTNERS.ORG
      • Principal Investigator: Rachel Jimenez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

->18 years of age

• Non-metastatic Breast Cancer patients who are scheduled to receive conventional left breast/chest wall RT inclusive of treatment to the internal mammary lymph nodes (IMNs)
• Prior chemotherapy is permitted
• Patients must have Left-sided Breast Cancer
• Ability to understand and the willingness to sign a written informed consent document
• No contraindication to MRI

Exclusion Criteria:

• Person who is pregnant or breastfeeding.
• Patient unable to swallow oral medication.
• Patients receiving any other investigational agent will not be excluded from study eligibility, unless the patient is already enrolled in an interventional study evaluating cardiac toxicity
• Patients already receiving ACE/ARBs.
• Patients with a history of allergic reactions to Losartan biosimilars.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation Therapy and Losartan; Participants will receive radiation therapy 5x weekly over 1-6 weeks. Participants will receive Losartan 1x daily during radiation therapy and for up to 6 months afterward then be followed for 1 year	Drug: Losartan; Taken Orally; Other Names: Losartan Potassium; Radiation: Radiation Therapy; Photon Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular Volume (ECV) of Myocardial Fibrosis	The primary endpoint is detectable decrease in extracellular volume as measured by cardiac MRI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum cardiac biomarker	The secondary objective of this study is to compare pre- and post-Radiation Therapy changes in serum TGF-β levels	6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Rachel Jimenez, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Myocardial Fibrosis; Radiation-Induced Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Radiation Injuries; Fibrosis; Heart Failure; Radiation Fibrosis Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 22-457

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes