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Radiation Fibrosis Syndrome

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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.

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.

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.

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.

Losartan 25 milligram capsule

Placebo

Katie Hess, Bachelors

Paige Bordelon, MPH

Patricia H Hardenbergh, MD

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.

This single site study will be conducted at the 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.

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.

Participants, research staff and clinicians will be blinded from study group assignment.

Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

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

There is no plan to share individual participant data (IPD) with other researchers.

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

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.

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.

Bilateral mammographic determination of breast volume will be calculated at routine follow-up intervals. Breast shrinkage associated with radiation-induced fibrosis will be assessed by monitoring the change in the breast volume of the treated breast from baseline to 18 months following completion of radiation therapy. Measurement of breast volume on both breasts will use breast height in centimeters (cm) (H), breast width in cm (W) and compression thickness in cm (C), from a craniocaudal projection. Volume in milliliters (mL) = (π/4) x H x W x C. Mammograms will also provide a distance measurement, in centimeters, on the nipple line from nipple to pectoralis muscle and a length measurement, in centimeters, from the superior to inferior margin that bisects the Posterior to Nipple Line (PNL) at a 90° angle.

Cosmesis will be assessed using a clinician assessment The Harvard Cosmesis Scale: 1=Excellent (Treated breast nearly identical to untreated breast); 2=Good (Treated breast slightly different from untreated breast); 3=Fair (Treated breast clearly different from untreated breast but not distorted); 4=Poor Treated breast seriously distorted.

Self-reported participant quality of life will be assessed by Breast-Q Reconstruction Module. The Breast-Q, Version 2.0 tool was developed to assess participant's perception of clinical outcomes in both psychological and satisfaction domains will be used.

* Psychosocial Well-Being module: measures psychological well being
* Physical Well-Being
* Chest module: measures pain or tightness and difficulty with mobility
* Satisfaction with Breasts (Post-Op) module: satisfaction with breast size, how bras fit, and appearance in mirror clothed or unclothed, as well as how breasts feel when they are touched.
* Adverse Effects of Radiation module: measures physical changes such as soreness of skin.

The participant's decision to have corrective surgery on either breast after radiation will be recorded at each time-point. Post-mastectomy patients will be considered to have been reoperated if corrective surgery occurred after permanent implant placement.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center

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