A Pilot Study of Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Fibrosis of the breast or reconstructed breast in irradiated breast cancer patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, research staff and clinicians will be blinded from study group assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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:
- •Other renin-angiotensin system (RAS) agent
- •Agents to increase serum potassium
- •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
研究组 & 干预措施
Breast Conservation Surgery with Losartan
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.
干预措施: Losartan 25 milligram capsule (Drug)
Breast Conservation Surgery with Placebo
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.
干预措施: Placebo (Drug)
Mastectomy with Losartan
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.
干预措施: Losartan 25 milligram capsule (Drug)
Mastectomy with Placebo
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Fibrosis of the breast or reconstructed breast in irradiated breast cancer patients
时间窗: Baseline, 3-, 6-, 12- and 18- month follow up visits
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
Average levels of cellular senescence, transforming growth factor beta-1 (TGF-β1) and senescence-associated secretory phenotype (SASP) serum biomarkers
时间窗: Baseline, day of last radiation therapy fraction, 3- and 12- month follow up visits
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.
Radiographic lung fibrosis in the radiation field of irradiated breast cancer patients
时间窗: Baseline, 3- and 12- month follow up visits
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.
次要结局
- Change in breast volume(Baseline, 6-, 12- and 18- month follow up visits)
- Cosmesis(Baseline, 3-, 6-, 12- and 18- month follow up visits)
- Patient reported outcomes(Baseline, 3-, 6-, 12- and 18-month follow up visits)
- Reoperation notation(Anytime from completion of radiation therapy assessed at 6-, 12- and 18-month follow up visits)
研究者
Patricia Hardenbergh
Medical Director
Shaw Cancer Center