Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Inflammation

Fibrosis

Radiation Injuries

Radiation Fibrosis Syndrome

Pneumonia

Radiation Pneumonitis

Syndrome

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Lung Injury

Camurati-Engelmann Disease

Anti-Arrhythmia Agents

Antihypertensive Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Micronutrients

Antineoplastic Agents

Vitamins

Losartan

Angiotensin Receptor Antagonists

Mitogens

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin-Converting Enzyme Inhibitors

Vitamin A

Retinol palmitate

Angiotensin II Type 1 Receptor Blockers

Retinol

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.

Steadman Philippon Research Institute

Shaw Cancer Center

Medical Director

Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination

Patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination

Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.

RNA sequencing

Analysis of RNA-seq data using the Oncobox algorithm.

Transcriptome analysis

target drug with the score above 0,1

target drug with the score equal or below 0,1

non-target drug

palliative care

Anton A Buzdin, Ph.D., D.Sc

This is a prospective trial for a computation-based efficacy prediction method for anticancer target therapies. The original computational algorithm utilizes individual transcriptome data of a cancer sample and assesses changes at the level of gene expression and intracellular signaling pathways. By applying the database of known molecular targets of anticancer target drugs it allows to rank potential efficacies of target drugs.

Original computational algorithm Oncobox was developed to determine molecular features of individual tumors. It represents the solution for a personalized selection of target anticancer therapies. The method is based on the analysis of gene expression profile of a cancer sample in comparison with the corresponding normal tissue biosamples in order to select the most effective molecular targets for their inhibition and, accordingly, to identify more effective target drugs for cancer treatment. Histological material obtained from cancer patients during surgery or core-needle biopsy as part of standard treatment will be used for the analysis. Total RNA extracted from the tumor material will be subjected to next-generation sequencing (NGS). By comparing transcriptome profile of the tumor sample with the profiles of the corresponding normal tissue samples the rate of molecular pathways activation/deactivation will be calculated, as well as the case-to-normal ratios for the individual gene products - molecular targets of drugs. Based on these data, each target drug will be assigned with a score reflecting its potential efficacy for each individual tumor treatment. A drug with the score value above 0.1 will be considered potentially effective, a drug with the score value equal to or below 0.1 - as potentially ineffective. Following Oncobox test, 130 target anticancer drugs will be rated according to their predicted effectiveness (see the list of eligible target drugs below). This information will be fully available to a patient and his/her doctor. The doctor will prescribe treatment according to his/her consideration, e.g. based on the standards of care and the patient's life indications. After the appointment of therapy, the patients will be divided naturally into the following three observation groups. The first group will be formed from patients receiving target drugs with the score value above 0,1 as monotherapy or in combination. The second group - patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination. Third group will be formed by patients receiving palliative care. Within this study, these three groups will be compared by response to the therapy according to the results of instrumental studies, by time to progression and by time to progression compared to the previous line of therapy (if any). Additionally, overall survival will be measured in all three groups.

Eligible target drugs:

1. Abemaciclib (LY2835219)
2. Afatinib
3. Aflibercept
4. Alectinib
5. Alemtuzumab
6. Alitretinoin
7. Anastrozole
8. Apalutamide, ARN-509
9. Arsenic trioxide
10. Atezolizumab
11. Avelumab
12. Axitinib
13. Belinostat
14. Bevacizumab
15. Bexarotene
16. Bicalutamide
17. Binimetinib (MEK162)
18. Blinatumomab
19. Bortezomib
20. Bosutinib
21. Brentuximab vedotin
22. Brigatinib
23. Cabazitaxel
24. Cabozantinib
25. Carfilzomib
26. Ceritinib (Zykadia, LDK378)
27. Cetuximab
28. Cobimetinib
29. Crizotinib
30. CYT387 (Momelotinib)
31. Dabrafenib
32. Daratumumab
33. Dasatinib
34. Degarelix
35. Denileukin diftitox (Ontac)
36. Denosumab
37. Docetaxel
38. Dovitinib
39. Durvalumab
40. Elotuzumab
41. Encorafenib
42. Enzalutamide
43. Erlotinib
44. Estramustine
45. Everolimus
46. Exemestane
47. Flavopiridol (Alvociclib)
48. Foretinib
49. Fulvestrant
50. Ganetespib (STA-9090)
51. Gefitinib
52. Goserelin
53. Homoharringtonine (Omacetaxine mepesuccinate)
54. Ibritumomab tiuxetan
55. Ibrutinib
56. Idelalisib
57. Imatinib
58. Inotuzumab ozogamicin
59. Ipilimumab
60. Ixabepilone
61. Ixazomib (MLN9708)
62. Lapatinib
63. Lenalidomide
64. Lenvatinib
65. Letrozole
66. Leuprolide
67. Lomustine
68. Masitinib
69. Medroxyprogesterone acetate (MPA)
70. Megestrol
71. Methyltestosterone
72. Midostaurin
73. Mogamulizumab
74. Moxetumomab pasudotox
75. Necitumumab
76. Nilotinib
77. Nilutamide
78. Nimotuzumab
79. Nintedanib (BIBF 1120)
80. Niraparib
81. Nivolumab (BMS-936558)
82. Obinutuzumab
83. Ofatumumab
84. Olaparib
85. Olaratumab
86. Osimertinib
87. Paclitaxel
88. Palbociclib
89. Panitumumab
90. Panobinostat
91. Pazopanib
92. Pembrolizumab
93. Perifosine
94. Pertuzumab
95. Pomalidomide
96. Ponatinib
97. Ramucirumab (Cyramza)
98. Regorafenib
99. Ribociclib
100. Rigosertib
101. Rituximab
102. Romidepsin
103. Rucaparib
104. Ruxolitinib
105. Selumetinib
106. Siltuximab
107. Sonidegib (LDE225)
108. Sorafenib
109. Sunitinib
110. Tamoxifen
111. Tecemotide (Emepepimut-S, L-BLP25)
112. Temozolomide
113. Temsirolimus
114. Thalidomide
115. Tivantinib
116. Tivozanib
117. Toremifene
118. Trametinib (Mekinst)
119. Trastuzumab
120. Trebananib
121. Vandetanib
122. Veliparib
123. Vemurafenib
124. Venetoclax
125. Vinblastine
126. Vincristine
127. Vindesine
128. Vinorelbine
129. Vismodegib
130. Vorinostat

Formalin-fixed, paraffin-embedded pathological cancer samples obtained during surgery or core needle biopsy

Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy

Study Protocol, Statistical Analysis Plan (SAP), NGS data, Clinical Study Report (CSR)

Tumor response according to the results of instrumental studies

Time to progression compared to the previous therapy lane

Oncobox Ltd

Vitamed LLC

N.N. Blokhin National Medical Research Center of Oncology

Kaluga Regional Clinical Oncology Center

Multidisciplinary medical holding SM-Clinic

Oncological Clinical Dispensary No. 1 of the Moscow City Health Department

OmicsWay Corp.

Breast Diseases

Skin Diseases

Trastuzumab

Antineoplastic Agents, Immunological

Her2-positive breast cancer patients treated with Trastuzumab (monotherapy)

Her2-positive breast cancer patients treated with Trastuzumab in combination with other regimens of chemotherapy

Standard Trastuzumab treatment regimen recommended for breast cancer

Standard chemotherapy regimen recommended for breast cancer

Chemotherapy

The purpose of the study is to identify molecular markers at the level of molecular pathway activation to predict efficacy of anti-HER2 therapy with Trastuzumab.

Biopsy and/or surgical samples from Her2-positive breast cancer patients treated with Trastuzumab alone or in combinations with other regimens of chemotherapy with known clinical outcomes will be collected and subjected to mRNA sequencing. Expression profiles will be analysed using original bioinformatic platform Oncobox. Based on comparison of molecular pathways activation strength and clinical response to Trastuzumab and chemotherapy, this study aims to identify molecular markers predicting efficacy of therapy with Trastuzumab and the possibility of further relapse.

Formalin-fixed, paraffin embedded pathological samples of breast cancer obtained during radical mastectomy or core needle biopsy

Molecular Pathway Activation Markers Predicting Efficacy of Trastuzumab Therapy for HER2-positive Breast Cancer

Study Protocol Statistical Analysis Plan (SAP) NGS data Clinical Study Report (CSR)

Tumor response by RECIST v1.1 or pathological response according to Chevallier system

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center
Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy	NCT03724097	Cancer	RNA sequencing Transcriptome a... target drug wit... target drug wit... non-target drug palliative care	18 Years - 80 Years	OmicsWay Corp.
Molecular Pathway Activation Markers Predicting Efficacy of Trastuzumab Therapy for HER2-positive Breast Cancer	NCT03521245	HER2-positive B...	RNA sequencing Transcriptome a... Trastuzumab Chemotherapy	18 Years - 80 Years	OmicsWay Corp.
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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