A Pilot Study of Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

2022-155

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.

2023-08-17

2027-08-17

2027-08-17

Recruiting

Early phase I

40

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 or history of prior breast radiation therapy * Breast cancer requiring bilateral breast/chest wall radiation therapy * Undergoing concurrent chemotherapy treatment * Documented fall risk * Active known or suspected systemic autoimmune disease (except for vitiligo, residual auto-immune hypothyroidism requiring hormone replacement only, psoriasis not requiring systemic treatment for two years, conditions not expected to recur in the absence of an external trigger) or any history of a systemic inflammatory arthritis such as psoriatic, rheumatoid, systemic lupus, ankylosing spondylitis or reactive arthritis * Uncontrolled intercurrent illness including, but not limited to: * 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 * The presence of interstitial lung disease on baseline CT scan 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "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.\n\nAssessments 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.", 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Participants, research staff and clinicians will be blinded from study group assignment.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 40, 'type': 'ESTIMATED'}}

2023-10-16