Determinants of Resistance to Endocrine Therapy and a Cyclin-dependent Kinases 4 and 6 (CDK4/6) Inhibitor for HR+ MBC

NCT ID: NCT03439735

Last Updated: 2025-08-12

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-20

Study Completion Date

2026-11-01

Brief Summary

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

The goal of this research study is to determine if the investigators can predict which participants will respond to endocrine therapy and a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor for metastatic breast cancer and which participants will not. Investigators will use information from the tumor tissue and serial blood samples. Investigators hope that a deeper understanding of which participants will respond to this combination and how resistance emerges will allow the investigators to better tailor therapies for metastatic breast cancer.

Subjects will have archived tissue or new biopsy collected at study enrollment. This tissue will undergo special molecular testing. Subjects will also have blood collected at study enrollment and periodically thereafter. This blood will also undergo special molecular testing. Information from this testing will not be available to subjects or their treating physicians as the investigators do not know how this information should impact treatment.

The investigators will collect information about which treatment the subjects receive and how their cancer responds.

Any man or woman being seen at Johns Hopkins for treatment of newly diagnosed estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) metastatic breast cancer may be eligible.

Detailed Description

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

Resistance to endocrine therapy (ET) invariably develops in patients with estrogen and/or progesterone receptor (ER/ PR) positive metastatic breast cancer (MBC). Data regarding primary resistance and patterns of emergence of acquired resistance in patients treated with endocrine therapy (ET) and cyclin dependent kinase 4 and 6 (CDK4/6) inhibitors are limited. Understanding these mechanisms could result in improved selection of treatment options and provide new targets for therapy development. In this study, we aim to identify and characterize determinants of intrinsic and acquired resistance to endocrine therapy in patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative MBC treated with the combination of endocrine therapy (aromatase inhibitor or fulvestrant) and a CDK4/6 inhibitor.

Investigators will determine the prevalence of genomic alterations at baseline in the primary tumor, metastatic tissue and plasma tumor DNA (ptDNA), including in the gene encoding estrogen receptor- alpha (ESR1). The mutational tumor burden in the primary tumor, metastatic tumor and blood will be assessed. Blood samples will be collected at several time points, allowing the detection of changes in molecular markers over time. We will further characterize tissue markers associated with progression and duration of response by evaluating these markers in available tissue obtained at progression. Investigators goal is to evaluate the prevalence and role of known alterations determining endocrine resistance in patients with metastatic disease, as knowledge regarding this population remains limited.The investigators also hope to unveil novel markers of endocrine resistance.

Conditions

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

Breast Cancer

Study Design

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

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6

Participants will undergo blood collection (intervention) at time of initiating treatment with endocrine therapy and palbociclib, at 4 weeks after initiating this treatment, and every 3-4 months while on treatment. If a participant progresses on this treatment, they will have a blood collection at that time.

Group Type EXPERIMENTAL

Endocrine Therapy and a CDK 4/6 inhibitor

Intervention Type DRUG

Participants with untreated metastatic disease receiving ET and a CDK 4/6 i as first line therapy.

Endocrine Therapy and a CDK 4/6 inhibitor

Intervention Type DRUG

Participants initiating a CDK 4/6 i after progression on ET.

Cohort B: Participants initiating a CDK 4/6 i after progression on ET.

Participants will undergo blood collection (intervention) at time of initiating treatment with endocrine therapy and palbociclib, at 4 weeks after initiating this treatment, and every 3-4 months while on treatment. If a participant progresses on this treatment, they will have a blood collection at that time.

Group Type EXPERIMENTAL

Endocrine Therapy and a CDK 4/6 inhibitor

Intervention Type DRUG

Participants with untreated metastatic disease receiving ET and a CDK 4/6 i as first line therapy.

Endocrine Therapy and a CDK 4/6 inhibitor

Intervention Type DRUG

Participants initiating a CDK 4/6 i after progression on ET.

Interventions

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

Endocrine Therapy and a CDK 4/6 inhibitor

Participants with untreated metastatic disease receiving ET and a CDK 4/6 i as first line therapy.

Intervention Type DRUG

Endocrine Therapy and a CDK 4/6 inhibitor

Participants initiating a CDK 4/6 i after progression on ET.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ET and CDK4/6i ET and CDK4/6i

Eligibility Criteria

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

Inclusion Criteria

* Male or Female
* 18 years or older
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Metastatic (stage IV) breast cancer or locally advanced breast cancer
* Estrogen Receptor (ER) and/or Progesterone Receptor (PR) positive, HER2- negative
* Treatment naïve in metastatic or locally advanced setting and planning to undergo treatment with endocrine therapy (ET) and palbociclib OR receiving first-line ET and palbociclib for metastatic or locally advanced disease.
* Premenopausal women and men must be treated with concurrent luteinizing hormone-releasing hormone (LHRH) agonist as would be standard-of-care.
* Evaluable or measurable disease.
* Tissue from a metastatic site must be available within past 6 months prior to therapy initiation.
* Ability to give voluntary informed consent

Exclusion Criteria

* Any pregnant or nursing woman
* No history of another primary malignancy within past 5 years. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

Safeway Foundation

UNKNOWN

Sponsor Role collaborator

Biovica International AB

UNKNOWN

Sponsor Role collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Jessica Tao, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Countries

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

United States

Other Identifiers

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

IRB00143030

Identifier Type: OTHER

Identifier Source: secondary_id

J17118

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

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