Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

Shaw Cancer Center

Status and phase: Enrolling; Phase 2

Conditions: Radiation Induced Fibrosis

Treatments: Drug: Losartan 25 milligram capsule; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05637216

2022-155

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 40 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 4 patient groups, including a placebo group

Breast Conservation Surgery with Losartan

Experimental group

Description:

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.

Treatment:

Drug: Losartan 25 milligram capsule

Breast Conservation Surgery with Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Mastectomy with Losartan

Experimental group

Description:

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.

Treatment:

Drug: Losartan 25 milligram capsule

Mastectomy with Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo