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Radiation Induced FibrosisPhase 2NCT05637216

Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

A Phase 2 study testing Losartan 25 milligram capsule in people with Radiation Induced Fibrosis, run by Shaw Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Radiation Induced Fibrosis
What is being tested?
Losartan 25 milligram capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
43 participants
Where
1 siteUnited States
Study dates
17 Aug 2023to 17 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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.

Who cannot join

  • 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:
Show all 29Show fewer
  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • Vail Health Shaw Cancer Center

    Edwards, Colorado, 81632

Other trials in United States

About this study

Official title: A Pilot Study of 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.

Read the detailed 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.

Being tested
Losartan 25 milligram capsule, Placebo
Keywords
losartan, radiation, fibrosis, cosmesis, reoperation, TGFB1, Transforming growth factor beta 1 (TGF-β1), Angiotensin II Receptor Blockers, ace inhibitor, Angiotensin-converting enzyme (ACE) inhibitors, TGF-β1, antifibrotic, signaling pathway, breast cancer, TGF beta, radiation induced fibrosis, irradiation fibrosis, Radiation injury with fibrosis, Transforming growth factor beta 1, Inflammation
Medical subject headings
Radiation Fibrosis Syndrome, Fibrosis, Camurati-Engelmann Syndrome, Breast Neoplasms, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Losartan 25 milligram capsuleDrug

    Also called losartan potassium

    Losartan 25 milligram oral capsule

  • PlaceboDrug

    Placebo 25 milligram oral capsule

Study groups in NCT05637216
Study groupRoleWhat they receive
Breast Conservation Surgery with LosartanExperimentalParticipants 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.
Receives: Drug: Losartan 25 milligram capsule
Breast Conservation Surgery with PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo
Mastectomy with LosartanExperimentalParticipants 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.
Receives: Drug: Losartan 25 milligram capsule
Mastectomy with PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fibrosis of the breast or reconstructed breast in irradiated breast cancer patients

    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

    Measured: Baseline, 3-, 6-, 12- and 18- month follow up visits

  2. Radiographic lung fibrosis in the radiation field of irradiated breast cancer patients

    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.

    Measured: Baseline, 3- and 12- month follow up visits

  3. Average levels of cellular senescence, transforming growth factor beta-1 (TGF-β1) and senescence-associated secretory phenotype (SASP) serum biomarkers

    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.

    Measured: Baseline, day of last radiation therapy fraction, 3- and 12- month follow up visits

Secondary outcomes (4)

  1. Change in breast volume

    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.

    Measured: Baseline, 6-, 12- and 18- month follow up visits

  2. Cosmesis

    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.

    Measured: Baseline, 3-, 6-, 12- and 18- month follow up visits

  3. Patient reported outcomes

    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.

    Measured: Baseline, 3-, 6-, 12- and 18-month follow up visits

  4. Reoperation notation

    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.

    Measured: Anytime from completion of radiation therapy assessed at 6-, 12- and 18-month follow up visits

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2022
  2. Study start17 Aug 2023
  3. Primary completion17 Aug 2027 (estimated)
  4. Study completion17 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
43 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05637216
Sponsor's protocol ID
2022-155
Status last verified
Jun 2026
First submitted
10 Nov 2022
Last updated
18 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: There is no plan to share individual participant data (IPD) with other researchers.

Publications

  • McCormick B, Winter KA, Woodward W, Kuerer HM, Sneige N, Rakovitch E, Smith BL, Germain I, Hartford AC, O'Rourke MA, Walker EM, Strom EA, Hopkins JO, Pierce LJ, Pu AT, Sumida KNM, Vesprini D, Moughan J, White JR. Randomized Phase III Trial Evaluating Radiation Following Surgical Excision for Good-Risk Ductal Carcinoma In Situ: Long-Term Report From NRG Oncology/RTOG 9804. J Clin Oncol. 2021 Nov 10;39(32):3574-3582. doi: 10.1200/JCO.21.01083. Epub 2021 Aug 18.

    PubMed 34406870

  • Collette S, Collette L, Budiharto T, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad W, Mueller RP, Kurtz J, Morgan DA, Dubois JB, Salamon E, Mirimanoff R, Bolla M, Van der Hulst M, Warlam-Rodenhuis CC, Bartelink H; EORTC Radiation Oncology Group. Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC Trial 22881-10882 'boost versus no boost'. Eur J Cancer. 2008 Nov;44(17):2587-99. doi: 10.1016/j.ejca.2008.07.032. Epub 2008 Aug 29.

    PubMed 18757193

  • Karlsen J, Tandstad T, Sowa P, Salvesen O, Stenehjem JS, Lundgren S, Reidunsdatter RJ. Pneumonitis and fibrosis after breast cancer radiotherapy: occurrence and treatment-related predictors. Acta Oncol. 2021 Dec;60(12):1651-1658. doi: 10.1080/0284186X.2021.1976828. Epub 2021 Oct 7.

    PubMed 34618657

  • Grossberg 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.

    PubMed 30027292

  • Akhurst RJ, Hata A. Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct;11(10):790-811. doi: 10.1038/nrd3810. Epub 2012 Sep 24.

    PubMed 23000686

  • Boothe DL, Coplowitz S, Greenwood E, Barney CL, Christos PJ, Parashar B, Nori D, Chao KS, Wernicke AG. Transforming growth factor beta-1 (TGF-beta1) is a serum biomarker of radiation induced fibrosis in patients treated with intracavitary accelerated partial breast irradiation: preliminary results of a prospective study. Int J Radiat Oncol Biol Phys. 2013 Dec 1;87(5):1030-6. doi: 10.1016/j.ijrobp.2013.08.045. Epub 2013 Oct 16.

    PubMed 24139518

  • Anscher MS. Targeting the TGF-beta1 pathway to prevent normal tissue injury after cancer therapy. Oncologist. 2010;15(4):350-9. doi: 10.1634/theoncologist.2009-S101.

    PubMed 20413640

  • Li C, Wilson PB, Levine E, Barber J, Stewart AL, Kumar S. TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer. 1999 Apr 20;84(2):155-9. doi: 10.1002/(sici)1097-0215(19990420)84:23.0.co;2-s.

    PubMed 10096248

  • Katzel EB, Koltz PF, Tierney R, Williams JP, Awad HA, O'Keefe RJ, Langstein HN. The impact of Smad3 loss of function on TGF-beta signaling and radiation-induced capsular contracture. Plast Reconstr Surg. 2011 Jun;127(6):2263-2269. doi: 10.1097/PRS.0b013e3182131bea.

    PubMed 21617460

  • Zhang M, Zhang YY, Chen Y, Wang J, Wang Q, Lu H. TGF-beta Signaling and Resistance to Cancer Therapy. Front Cell Dev Biol. 2021 Nov 30;9:786728. doi: 10.3389/fcell.2021.786728. eCollection 2021.

    PubMed 34917620

  • Gans I, El Abiad JM, James AW, Levin AS, Morris CD. Administration of TGF-ss Inhibitor Mitigates Radiation-induced Fibrosis in a Mouse Model. Clin Orthop Relat Res. 2021 Mar 1;479(3):468-474. doi: 10.1097/CORR.0000000000001286.

    PubMed 33252888

  • Kobayashi M, Ota S, Terada S, Kawakami Y, Otsuka T, Fu FH, Huard J. The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries. Am J Sports Med. 2016 Dec;44(12):3252-3261. doi: 10.1177/0363546516656823. Epub 2016 Aug 8.

    PubMed 27501834

  • Kovacs MG, Kovacs ZZA, Varga Z, Szucs G, Freiwan M, Farkas K, Kovari B, Cserni G, Kriston A, Kovacs F, Horvath P, Foldesi I, Csont T, Kahan Z, Sarkozy M. Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease. Int J Mol Sci. 2021 Nov 30;22(23):12963. doi: 10.3390/ijms222312963.

    PubMed 34884782

  • Bar-Klein G, Cacheaux LP, Kamintsky L, Prager O, Weissberg I, Schoknecht K, Cheng P, Kim SY, Wood L, Heinemann U, Kaufer D, Friedman A. Losartan prevents acquired epilepsy via TGF-beta signaling suppression. Ann Neurol. 2014 Jun;75(6):864-75. doi: 10.1002/ana.24147. Epub 2014 May 28.

    PubMed 24659129

  • Lipworth L, Abdel-Kader K, Morse J, Stewart TG, Kabagambe EK, Parr SK, Birdwell KA, Matheny ME, Hung AM, Blot WJ, Ikizler TA, Siew ED. High prevalence of non-steroidal anti-inflammatory drug use among acute kidney injury survivors in the southern community cohort study. BMC Nephrol. 2016 Nov 24;17(1):189. doi: 10.1186/s12882-016-0411-7.

    PubMed 27881100

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Losartan 25 milligram capsule in people with Radiation Induced Fibrosis, run by Shaw Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fibrosis of the breast or reconstructed breast in irradiated breast cancer patients (time frame: Baseline, 3-, 6-, 12- and 18- month follow up visits). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05637216, which also lists 98 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.

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