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

NCT03439735 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: J17118IRB00143030
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Metastatic Breast Cancer; Aromatase Inhibitors; Palbociclib; Hormone Receptor Positive Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Genetic Mutation

  The number of participants who have an ESR1 mutation prior to receiving endocrine therapy and palbociclib.

  2 years

Secondary Outcomes (2)

• Genetic Mutation

  4 years

• Genetic Mutation

  3 years

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: Endocrine Therapy and a CDK 4/6 inhibitor

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

EXPERIMENTAL

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.

Drug: Endocrine Therapy and a CDK 4/6 inhibitor

Interventions

Endocrine Therapy and a CDK 4/6 inhibitor DRUG

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

Also known as: ET and CDK4/6i

Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6; Cohort B: Participants initiating a CDK 4/6 i after progression on ET.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Safeway Foundation: collaborator
• Biovica International AB: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Jessica Tao, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: February 20, 2018
• Study Start: July 20, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)