Understanding resistance to hormone therapy and CDK4/6 inhibitors in metastatic breast cancer

Prospective Evaluation of Determinants of Resistance to Endocrine Therapy and a Cyclin-dependent Kinases 4 and 6 (CDK4/6) Inhibitor in Hormone Receptor (HR) Positive Metastatic Breast Cancer (MBC)

Phase 2 Interventional Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · NCT03439735

This study is testing how well hormone therapy and a specific drug work for people with advanced breast cancer and aims to find out why some patients don’t respond to these treatments.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years to 100 Years
SexAll
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins Academic / other
Locations1 site (Baltimore, Maryland)
Trial IDNCT03439735 on ClinicalTrials.gov

What this trial studies

This research aims to identify which patients with hormone receptor positive metastatic breast cancer will respond to endocrine therapy and a CDK4/6 inhibitor, and to understand the mechanisms behind resistance to these treatments. Participants will provide tumor tissue and blood samples for molecular testing to assess genomic alterations and mutational tumor burden. The study will track changes in molecular markers over time to better tailor therapies for patients. Ultimately, the goal is to improve treatment selection and develop new therapeutic targets based on the findings.

Who should consider this trial

Good fit: Ideal candidates include adults with hormone receptor positive, HER2 negative metastatic breast cancer who are either treatment naïve or receiving first-line therapy.

Not a fit: Patients who are pregnant, nursing, or have a history of another primary malignancy within the past five years may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective treatment options for patients with metastatic breast cancer.

How similar studies have performed: Other studies have shown promise in understanding resistance mechanisms in breast cancer, but this specific approach is novel and aims to provide deeper insights.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Baltimore, Maryland

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Breast CancerMetastatic Breast CancerAromatase InhibitorsPalbociclibHormone Receptor Positive Metastatic Breast Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.