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

NCT ID: NCT05814224

Last Updated: 2023-04-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-22

Study Completion Date

2024-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Patients with hormone receptor-positive MBC are eligible for endocrine therapy (ET) as first line treatment which is based on strategies aimed to either block signaling pathways depending on the estrogen receptor (ESR1) or using ESR1 antagonists. Only a few accepted predictive factors are associated with treatment benefit for MBC (i.e., hormone receptor status and HER2 status). Furthermore, a standardized assessment evaluation for MBC is still lacking. Because of these unmet needs, ET is continued until disease progression, or if toxicity requiring discontinuation occurs. Resistance is frequent in the treatment of early BC and unavoidable in MBC. Recently, mutations in ESR1 have been described in MBC that had been previously exposed to aromatase inhibitors (AIs) and are rarely detectable in primary BC. Besides that, resistance phenomena have been also linked to ESR1 cisregulatory elements (CRE, i.e. enhancers and promoters) hypermethylation, both related to ESR1 silencing.

According to the literature, the aim of the study is to detect tumor response with liquid biopsy technique compared to conventional clinical pratice algorithms.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hormone-receptor positive MBC

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

Group Type EXPERIMENTAL

Liquid biopsy and CT scan

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Liquid biopsy and CT scan

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Centro di Riferimento Oncologico - Aviano

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Fabio Puglisi, MD

Role: PRINCIPAL_INVESTIGATOR

Centro di Riferimento Oncologico - Aviano

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Asst Papa Giovanni Xxiii- Bergamo

Bergamo, Bergamo, Italy

Site Status RECRUITING

Centro di Riferimento Oncologico - Aviano

Aviano, Pordenone, Italy

Site Status RECRUITING

Asst Ospedali Civili Di Brescia

Brescia, , Italy

Site Status RECRUITING

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

Catania, , Italy

Site Status RECRUITING

Universita' Degli Studi Di Napoli Federico Ii

Napoli, , Italy

Site Status RECRUITING

azienda sanitaria universitaria friuli centrale- Udine

Udine, , Italy

Site Status RECRUITING

Ospedale San Bortolo- Azienda Ulss8 Berica

Vicenza, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Fabio Puglisi, MD

Role: CONTACT

0434 659310

Elisa De Crignis, PhD

Role: CONTACT

0434-659077

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

CARLO ALBERTO TONDINI

Role: primary

Fabio Puglisi, MD

Role: primary

0434 659310

Elisa De Crignis, PhD

Role: backup

0434 659077

VITO AMOROSO

Role: primary

PAOLO VIGNERI

Role: primary

MARIO GIULIANO

Role: primary

MARTA BONOTTO

Role: primary

LAURA MERLINI

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 27837704 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24185512 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24398047 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26560360 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27270325 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11880477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24495356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26169690 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17374832 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24794159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26018662 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27269946 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21955614 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18708351 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2018.016

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Locoregional Recurrence of Breast Cancer
NCT05988112 NOT_YET_RECRUITING
MRD in High-risk EBC
NCT06566729 ACTIVE_NOT_RECRUITING