Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

Sponsor

Shaw Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05637216

Collaborator

Steadman Philippon Research Institute (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo-controlled trial assessing Losartan in reducing radiation induced fibrosis in breast cancer patients undergoing standard of care radiation therapy after surgery.

Condition or Disease	Intervention/Treatment	Phase
Radiation Induced Fibrosis	Drug: Losartan 12.5milligram capsule Drug: Placebo	Phase 2

Detailed Description

This single site study will be conducted at the Shaw Cancer Center in Edwards, Colorado testing the hypothesis that Losartan will decrease the development of radiation induced fibrosis in breast cancer patients. A block, double-blinded, placebo-controlled, randomized phase II trial will be utilized to test this hypothesis.

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 12.5mg capsules of placebo or the study drug, Losartan, to be taken by mouth twice 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 two years following the completion of radiation therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This trial will use a double-blinded placebo-controlled design to blind both investigators and study participants to reduce bias due to the provider and participant assessed endpoints. This trial will use a dose of 12.5 milligram capsules taken by mouth twice daily for all participants. This protocol will compare participants on losartan to those on placebo but it will include separate arms for participants who received breast conservation surgery versus participants who received a mastectomy. Beyond separating the two surgery groups (1) breast conservation and (2) mastectomy, no further stratification will be included. Assessments will be made at baseline 3 months, 6 months, 12 moths, 18 months and 24 months from the completion of radiation therapy. These assessments will include provider assessments, mammography measurements and participant reported outcomes of fibrosis and cosmesis and the participant's decision for reoperation.This trial will use a double-blinded placebo-controlled design to blind both investigators and study participants to reduce bias due to the provider and participant assessed endpoints. This trial will use a dose of 12.5 milligram capsules taken by mouth twice daily for all participants. This protocol will compare participants on losartan to those on placebo but it will include separate arms for participants who received breast conservation surgery versus participants who received a mastectomy. Beyond separating the two surgery groups (1) breast conservation and (2) mastectomy, no further stratification will be included. Assessments will be made at baseline 3 months, 6 months, 12 moths, 18 months and 24 months from the completion of radiation therapy. These assessments will include provider assessments, mammography measurements and participant reported outcomes of fibrosis and cosmesis and the participant's decision for reoperation.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

This double-blinded placebo controlled trial will use randomization of the losartan versus placebo and blind from participants and care providers.

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Breast Conservation Surgery with Losartan The study drug losartan 12.5 milligram capsule will be taken by mouth twice daily starting the day of radiation therapy until the follow up 1 year after finishing radiation therapy for participants who had breast conservation surgery.	Drug: Losartan 12.5milligram capsule The drug losartan will be used as a 12.5 milligram capsule taken by mouth twice daily. Losartan or its identical placebo will be randomized separately each to all breast conservation participants and to all mastectomy participants. Other Names: losartan potassium
Placebo Comparator: Breast Conservation Surgery with Placebo The study drug placebo 12.5 milligram capsule will be taken by mouth twice daily starting the day of radiation therapy until the follow up 1 year after finishing radiation therapy for participants who had breast conservation surgery.	Drug: Placebo The placebo will be a 12.5 milligram capsule identical in appearance to the interventional drug losartan.
Experimental: Mastectomy with Losartan The study drug losartan 12.5 milligram capsule will be taken by mouth twice daily starting the day of radiation therapy until the follow up 1 year after finishing radiation therapy for participants who had a mastectomy.	Drug: Losartan 12.5milligram capsule The drug losartan will be used as a 12.5 milligram capsule taken by mouth twice daily. Losartan or its identical placebo will be randomized separately each to all breast conservation participants and to all mastectomy participants. Other Names: losartan potassium
Placebo Comparator: Mastectomy with Placebo The study drug placebo 12.5 milligram capsule will be taken by mouth twice daily starting the day of radiation therapy until the follow up 1 year after finishing radiation therapy for participants who had a mastectomy.	Drug: Placebo The placebo will be a 12.5 milligram capsule identical in appearance to the interventional drug losartan.

Outcome Measures

Primary Outcome Measures

Late Effects Normal Tissue Task Force - Subjective, Objective, Management, Analytic Scale (LENT-SOMA) fibrosis assessment [Baseline, and at 3, 6, 12, 18 and 24 months following the end of radiation therapy]
The LENT-SOMA fibrosis sub scale assessment is a four-point ordinal grading system performed by healthcare professionals based on a patient interview and clinical assessment. For LENT-SOMA, zero (0) is the minimum score and denotes fibrosis not detectable. Zero is the best outcome in terms of fibrosis development. The maximum score is three (3) for LENT-SOMA and denotes very marked density, retraction and firmness and fixation of breast tissue. Three is the worst outcome for the patient in terms of fibrosis development.
Change in mammographic breast volume for breast conservation surgery patients [Baseline, and at 6, 12, 18 and 24 months following the end of radiation therapy]
Measurement of breast volume of both breasts will use breast height in centimeters (H), breast width in centimeters (W) and compression thickness in centimeters (C), from a craniocaudal projection. Volume (V) (in milliliters) = (π/4) x H x W x C.
Change in breast distance measurement on mammogram for breast conservation surgery patients [Baseline, and at 6, 12, 18 and 24 months following the end of radiation therapy]
Distance in centimeters, on the nipple line from nipple to pectorals muscle
Change in breast length measurement on mammogram for breast conservation surgery patients [Baseline, and at 6, 12, 18 and 24 months following the end of radiation therapy]
Distance in centimeters from the superior to inferior margin that bisects the posterior to nipple line (PNL) at a 90 degree angle

Secondary Outcome Measures

Breast-Q Reconstruction Module [Surveys will be completed by patients as baseline and at 3, 6, 12, 18 and 24 months following the end of radiation therapy]
The Breast-Q (version 2) modules measure patient's perceptions of clinical outcomes in both quality of life and satisfaction domains.
Harvard Breast Cosmesis Grading Scale [Baseline and at 3, 6, 12, 18 and 24 months following the end of radiation therapy]
The Harvard scale to evaluate cosmetic outcome is a four-point scale completed by a healthcare provider that describes the overall esthetic of the breasts as excellent, good, fair or poor.
Mammographic determination of symmetry in breast conservation surgery patients [Baseline and at 6, 12, 18 and 24 months following the end of radiation therapy.]
Measurement of breast volume of both breasts will use breast height in centimeters (H), breast width in centimeters (W) and compression thickness in centimeters (C), from a craniocaudal projection. Volume (V) (in milliliters) = (π/4) x H x W x C. The breast volume of the treated breast will be compared to the volume of the untreated breast as a measure of symmetry.

Other Outcome Measures

Incidence of Reoperation [Two years following the completion of radiation therapy]
Patients may chose to return to surgery to correct a poor outcome that could be associated with radiation induced fibrosis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Inclusion of Women and Minorities: Women of any race and any ethnicity are eligible for this trial. Women who are pregnant or nursing are excluded from this trial.

Exclusion Criteria:

Recurrent breast cancer or history of prior breast radiation therapy
Breast cancer requiring bilateral breast/chest wall radiation therapy
Breast conservation surgery patients with contralateral breast reduction prior to radiation
History of post-surgical infection
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:

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:

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
Individuals known to possess DNA repair genes 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

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