Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

This single site study will be conducted at the Vail Health Shaw Cancer Center in Edwards, Colorado. A block, double-blinded, placebo-controlled, randomized phase II design will be utilized .

Study participants will be blocked by surgical intervention (breast conserving surgery vs. mastectomy) and then randomized, 1:1, into the treatment and control arms for a total of four study arms. The research team and study participants will be blinded to the study arm and a placebo will be used to reduce detection bias in the reporting of outcomes. Selection bias will be minimized through the randomization of study arms.

Study participants will be prescribed 25mg capsules of placebo or the investigational drug, Losartan, to be taken by mouth once daily. The treatment start date will be the day that subject begins radiation therapy. Radiation therapy will continue to be prescribed in accordance with local clinic procedures. Treatment with the study intervention will continue for one year upon completion of radiation therapy. All participants will be assessed for fibrosis, cosmetic outcomes, and incidence of reoperation for 18 months following the completion of radiation therapy.

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