Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

NCT05637216 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2022-155
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy of losartan (LOS), an FDA-approved transforming growth factor beta-1 (TGF-β1) blocker, to decrease radiation induced fibrosis (RIF) in the breast and the lung of breast cancer patients, testing the hypothesis that Losartan will decrease RIF, TGF- β1 and cellular senescence/inflammation in the breast and the lung of irradiated breast cancer patients relative to placebo treatment and consequently improve clinical outcomes in breast cancer patients.

Conditions

Radiation Induced Fibrosis

Keywords

losartan; radiation; fibrosis; cosmesis; reoperation; TGFB1; Transforming growth factor beta 1 (TGF-β1); Angiotensin II Receptor Blockers; ace inhibitor; Angiotensin-converting enzyme (ACE) inhibitors; TGF-β1; antifibrotic; signaling pathway; breast cancer; TGF beta; radiation induced fibrosis; irradiation fibrosis; Radiation injury with fibrosis; Transforming growth factor beta 1; Inflammation; Biomarker; Suppressor of Mothers against Decapentaplegic (SMAD)

Outcome Measures

Primary Outcomes (3)

• Fibrosis of the breast or reconstructed breast in irradiated breast cancer patients

  Fibrosis will be assessed by a radiation oncology provider using the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) scale. 0=Fibrosis absent, not detectable. 1=Fibrosis is Barely Palpable; 2=Definite increased density; 3=Very marked density, retraction and firmness and fixation

  Baseline, 3-, 6-, 12- and 18- month follow up visits

• Radiographic lung fibrosis in the radiation field of irradiated breast cancer patients

  Radiographic lung fibrosis will be assessed with high resolution CT scans of the thorax. Thorax CT scans will be fused to the radiation planning CT scan for confirmation of the overlap of fibrosis with the radiation field.

  Baseline, 3- and 12- month follow up visits

• Average levels of cellular senescence, transforming growth factor beta-1 (TGF-β1) and senescence-associated secretory phenotype (SASP) serum biomarkers

  Cellular senescence, and senescence-associated secretory phenotype (SASP) including TGF-β and inflammation will be quantified in the treatment and control group. A novel and expert approach to measure senescent cells in serum will be utilized.

  Baseline, day of last radiation therapy fraction, 3- and 12- month follow up visits

Secondary Outcomes (4)

• Change in breast volume

  Baseline, 6-, 12- and 18- month follow up visits

• Cosmesis

  Baseline, 3-, 6-, 12- and 18- month follow up visits

• Patient reported outcomes

  Baseline, 3-, 6-, 12- and 18-month follow up visits

• Reoperation notation

  Anytime from completion of radiation therapy assessed at 6-, 12- and 18-month follow up visits

Study Arms (4)

Breast Conservation Surgery with Losartan

EXPERIMENTAL

Participants who underwent breast conservation surgery will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Drug: Losartan 25 milligram capsule

Breast Conservation Surgery with Placebo

PLACEBO COMPARATOR

Participants who underwent breast conservation surgery will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Drug: Placebo

Mastectomy with Losartan

EXPERIMENTAL

Participants who underwent a mastectomy will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Drug: Losartan 25 milligram capsule

Mastectomy with Placebo

PLACEBO COMPARATOR

Participants who underwent a mastectomy will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Drug: Placebo

Interventions

Losartan 25 milligram capsule DRUG

Losartan 25 milligram oral capsule

Also known as: losartan potassium

Breast Conservation Surgery with Losartan; Mastectomy with Losartan

Placebo DRUG

Placebo 25 milligram oral capsule

Breast Conservation Surgery with Placebo; Mastectomy with Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosed with clinical or pathologic stage 0-IV invasive breast cancer to include ductal carcinoma in situ (Tis), primary tumor cannot be assessed (TX) and all other primary tumor stage categories (T1-T4)
• Has been treated with breast conserving surgery or mastectomy with reconstruction
• Is a candidate for unilateral post-surgery radiation therapy per National Comprehensive Cancer Network (NCCN) guidelines
• Age ≥ 18
• Female
• Laboratory values
• Aspartate Aminotransferase (AST) ≤ 2.5 x Upper Limit Normal (ULN)
• Alanine Aminotransferase (ALT) ≤ 2.5 x ULN
• Creatine ≤ 1.5 x ULN
• Estimated Glomerular Filtration Rate (eGFR) ≥ 60

You may not qualify if:

• Recurrent breast cancer and history of prior breast radiation therapy
• Breast cancer requiring bilateral breast/chest wall radiation therapy
• Undergoing concurrent chemotherapy treatment
• Documented fall risk
• Active known diagnosis of a connective tissue disorder, rheumatoid arthritis, or systemic lupus erythematosus (SLE)
• Any known uncontrolled intercurrent illness including, but not limited to:
• Hyperkalemia
• Impaired renal function
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Kidney disease
• Uncontrolled diabetes
• Cystic fibrosis
• Fibromyalgia based on American College of Rheumatology criteria
• Concomitant use of:

Sponsors & Collaborators

• Shaw Cancer Center: lead
• Steadman Philippon Research Institute: collaborator

Study Sites (1)

Vail Health Shaw Cancer Center

Edwards, Colorado, 81632, United States

RECRUITING

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MeSH Terms

Conditions

Radiation Fibrosis Syndrome; Fibrosis; Camurati-Engelmann Syndrome; Breast Neoplasms; Inflammation

Interventions

Losartan

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Radiation Injuries; Wounds and Injuries; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Patricia H Hardenbergh, MD

  Vail Health Shaw Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katie Hess, BS

CONTACT

(970) 485-7874; katherine.hess@vailhealth.org

Paige Bordelon, MPH

CONTACT

(970) 569-7806; paige.bordelon@vailhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, research staff and clinicians will be blinded from study group assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Model Details: Participants will be blocked by surgical type (breast conservation surgery/mastectomy) and then randomized 1:1 in a parallel design into treatment and control arms. All participants will take an oral 25 milligram tablet once daily of either losartan or placebo. Assessments of fibrosis will include provider assessments and participant reported outcomes of fibrosis and cosmesis, the participant's decision for reoperation, laboratory assessments of inflammatory biomarkers, a CT scan and bilateral mammograms.

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: December 5, 2022
• Study Start: August 17, 2023
• Primary Completion (Estimated): August 17, 2027
• Study Completion (Estimated): August 17, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)