Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA

NCT05814224 | Unknown DMC

• 1 other identifier: 2018.016
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of the study is to determine the diagnostic role of ctDNA when used to monitor metastatic breast cancer (MBC) during first-line endocrine therapy.

Conditions

Hormone Receptor Positive Breast Carcinoma; Breast Neoplasms; Neoplasms, Breast; Breast Diseases; Antineoplastic Agents; Aromatase Inhibitors; ESR1 Gene Mutation

Keywords

Epigenetics; Liquid biopsy; ctDNA; ESR1 Gene Mutation; Biomarker; HR-positive HER2-negative; Advanced breast cancer; CDK4/6; Antineoplastic Agents Hormonal

Outcome Measures

Primary Outcomes (1)

• Liquid-biopsy in monitoring treatment response in luminal breast cancer

  The primary objective of this study is to evaluate whether liquid-biopsy technique is able to detect treatment response in luminal breast cancer through the quantification of ESR1 ctDNA mutations

  3 years

Secondary Outcomes (12)

• ctDNA/miRNA based follow-up

  3 years

• Treatment resistance mechanisms

  3 years

• Specificity

  From baseline until disease progression

• Positive predictive value

  3 years

• Negative predictive value

  3 years

Study Arms (1)

Hormone-receptor positive MBC

EXPERIMENTAL

Women with hormone receptor-positive MBC, that will be eligible for endocrine therapy as first line treatment

Diagnostic Test: Liquid biopsy and CT scan

Interventions

Liquid biopsy and CT scan DIAGNOSTIC_TEST

CT scan and liquid biopsy blood sample are performed at baseline, after 8 weeks from baseline and, then, every 12 weeks. Between two subsequent CT scan another liquid biopsy blood sample is performed. CEA and CA 15.3 will be performed at baseline and then concomitantly to the radiological evaluation

Hormone-receptor positive MBC

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Females, 18 years of age or older
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease.
• ER positive tumor ≥ 1%
• HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio \< 2.0)
• Females, 18 years of age or older
• Candidate to first-line endocrine therapy (LH-RH analogue for premenopausal women is allowed)
• Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

You may not qualify if:

• Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Prior endocrine therapy for metastatic disease

Sponsors & Collaborators

• Centro di Riferimento Oncologico - Aviano: lead

Study Sites (7)

Asst Papa Giovanni Xxiii- Bergamo

Bergamo, Bergamo, Italy

RECRUITING

Centro di Riferimento Oncologico - Aviano

Aviano, Pordenone, 33081, Italy

RECRUITING

Asst Ospedali Civili Di Brescia

Brescia, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania

Catania, Italy

RECRUITING

Universita' Degli Studi Di Napoli Federico Ii

Napoli, Italy

RECRUITING

azienda sanitaria universitaria friuli centrale- Udine

Udine, Italy

RECRUITING

Ospedale San Bortolo- Azienda Ulss8 Berica

Vicenza, Italy

RECRUITING

Related Publications (14)

• Bonotto M, Gerratana L, Di Maio M, De Angelis C, Cinausero M, Moroso S, Milano M, Stanzione B, Gargiulo P, Iacono D, Minisini AM, Mansutti M, Fasola G, De Placido S, Arpino G, Puglisi F. Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis. Breast. 2017 Feb;31:114-120. doi: 10.1016/j.breast.2016.10.021. Epub 2016 Nov 9.

  PMID: 27837704 BACKGROUND

• Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013 Dec;45(12):1439-45. doi: 10.1038/ng.2822. Epub 2013 Nov 3.

  PMID: 24185512 BACKGROUND

• Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gomez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014 Apr 1;20(7):1757-1767. doi: 10.1158/1078-0432.CCR-13-2332. Epub 2014 Jan 7.

  PMID: 24398047 BACKGROUND

• Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, Fenwick K, Kozarewa I, Lopez-Knowles E, Ribas R, Nerurkar A, Osin P, Chandarlapaty S, Martin LA, Dowsett M, Smith IE, Turner NC. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015 Nov 11;7(313):313ra182. doi: 10.1126/scitranslmed.aac7551.

  PMID: 26560360 BACKGROUND

• Jansen MP, Martens JW, Helmijr JC, Beaufort CM, van Marion R, Krol NM, Monkhorst K, Trapman-Jansen AM, Meijer-van Gelder ME, Weerts MJ, Ramirez-Ardila DE, Dubbink HJ, Foekens JA, Sleijfer S, Berns EM. Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen. Oncotarget. 2016 Jul 12;7(28):43412-43418. doi: 10.18632/oncotarget.9727.

  PMID: 27270325 BACKGROUND

• Sasaki M, Tanaka Y, Perinchery G, Dharia A, Kotcherguina I, Fujimoto Si, Dahiya R. Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer. J Natl Cancer Inst. 2002 Mar 6;94(5):384-90. doi: 10.1093/jnci/94.5.384.

  PMID: 11880477 BACKGROUND

• Martinez-Galan J, Torres-Torres B, Nunez MI, Lopez-Penalver J, Del Moral R, Ruiz De Almodovar JM, Menjon S, Concha A, Chamorro C, Rios S, Delgado JR. ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients. BMC Cancer. 2014 Feb 4;14:59. doi: 10.1186/1471-2407-14-59.

  PMID: 24495356 BACKGROUND

• Stone A, Zotenko E, Locke WJ, Korbie D, Millar EK, Pidsley R, Stirzaker C, Graham P, Trau M, Musgrove EA, Nicholson RI, Gee JM, Clark SJ. DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer. Nat Commun. 2015 Jul 14;6:7758. doi: 10.1038/ncomms8758.

  PMID: 26169690 BACKGROUND

• Panageas KS, Ben-Porat L, Dickler MN, Chapman PB, Schrag D. When you look matters: the effect of assessment schedule on progression-free survival. J Natl Cancer Inst. 2007 Mar 21;99(6):428-32. doi: 10.1093/jnci/djk091.

  PMID: 17374832 BACKGROUND

• Bonotto M, Gerratana L, Poletto E, Driol P, Giangreco M, Russo S, Minisini AM, Andreetta C, Mansutti M, Pisa FE, Fasola G, Puglisi F. Measures of outcome in metastatic breast cancer: insights from a real-world scenario. Oncologist. 2014 Jun;19(6):608-15. doi: 10.1634/theoncologist.2014-0002. Epub 2014 May 2.

  PMID: 24794159 BACKGROUND

• Bonotto M, Gerratana L, Iacono D, Minisini AM, Rihawi K, Fasola G, Puglisi F. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines? Oncologist. 2015 Jul;20(7):719-24. doi: 10.1634/theoncologist.2015-0002. Epub 2015 May 27.

  PMID: 26018662 BACKGROUND

• Fribbens C, O'Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SR, Turner NC. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. J Clin Oncol. 2016 Sep 1;34(25):2961-8. doi: 10.1200/JCO.2016.67.3061. Epub 2016 Jun 6.

  PMID: 27269946 BACKGROUND

• Manavalan TT, Teng Y, Appana SN, Datta S, Kalbfleisch TS, Li Y, Klinge CM. Differential expression of microRNA expression in tamoxifen-sensitive MCF-7 versus tamoxifen-resistant LY2 human breast cancer cells. Cancer Lett. 2011 Dec 26;313(1):26-43. doi: 10.1016/j.canlet.2011.08.018. Epub 2011 Sep 10.

  PMID: 21955614 BACKGROUND

• Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008 Oct 31;283(44):29897-903. doi: 10.1074/jbc.M804612200. Epub 2008 Aug 15.

  PMID: 18708351 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Breast Diseases

Interventions

Liquid Biopsy; Tomography, X-Ray Computed

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Study Officials

• Fabio Puglisi, MD

  Centro di Riferimento Oncologico - Aviano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabio Puglisi, MD

CONTACT

0434 659310; fabio.puglisi@cro.it

Elisa De Crignis, PhD

CONTACT

0434-659077; elisa.decrignis@cro.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 14, 2023
• Study Start: May 22, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 1, 2024
• Last Updated: April 14, 2023

Record last verified: 2023-03

Locations

IT (7)