Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

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.

Sex

Female

Minimum age

18 Years

Inclusion Criteria

* 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

Inclusion of Women and Minorities - Women of any race/ethnicity are eligible for this trial.

Exclusion Criteria

* 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:

  * Losartan
  * Other renin-angiotensin system (RAS) agent
  * Agents to increase serum potassium
  * Lithium
  * Aliskiren for diabetes
* Having a known allergy to any active or inactive ingredient in Losartan
* Unable to tolerate oral medication
* Pregnant or breast-feeding or planning pregnancy for the year following radiation
* A medical history of interstitial lung disease or evidence of interstitial lung disease
* Patients with any medical condition, including findings in laboratory or medical history or in the baseline assessments, that (in the opinion of the Principal Clinical Investigator or his/her designee), constitutes a risk or contraindication for participation in the study or that could interfere with the study conduct, endpoint evaluation or prevent the subject from fully participating in all aspects of the study
* Individuals known to possess deoxyribonucleic acid (DNA) gene mutations including:

  * Ataxia-Telangiectasia Mutated (ATM)
  * Double-strand-break repair protein rad21 homolog (RAD21)
  * C-to-T single-nucleotide polymorphism (C-509T) in the Transforming growth factor β-1 gene

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• BACKGROUNDGrossberg AJ, Lei X, Xu T, Shaitelman SF, Hoffman KE, Bloom ES, Stauder MC, Tereffe W, Schlembach PJ, Woodward WA, Buchholz TA, Smith BD. Association of Transforming Growth Factor beta Polymorphism C-509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1751-1757. doi: 10.1001/jamaoncol.2018.2583. PMID 30027292
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