Determinants of Resistance to First-line Therapy With an AI and Palbociclib for HR+ MBC

  • STATUS
    Recruiting
  • End date
    Jul 1, 2022
  • participants needed
    100
  • sponsor
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Updated on 24 January 2021
estrogen
measurable disease
progesterone
advanced breast cancer
HER2
gonadotropin releasing hormone
progesterone receptor
stage iv breast cancer
erbb2
aromatase inhibitor
estrogen receptor
palbociclib
locally advanced breast cancer

Summary

The goal of this research study is to determine if the investigators can predict which participants will respond to an aromatase inhibitor and palbociclib 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.

Description

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 treatment nave patients treated with aromatase inhibitor (AI) 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, the investigators 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 an AI and the CDK4/6 inhibitor palbociclib in the first -line setting.

Investigators will determine the prevalence of genomic alterations at baseline in the primary tumor, metastatic tissue and plasma tumor DNA (ptDNA). This will include 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. The investigators will further characterize tissue markers associated with progression and duration of response by evaluating these markers in available tissue obtained at progression. The investigators goal is to evaluate the prevalence and role of known alterations determining endocrine resistance in patients previously untreated for metastatic disease, as knowledge regarding this population remains limited. The investigators also hope to unveil novel markers of endocrine resistance.

Details
Condition Breast Cancer, Breast Cancer Diagnosis, breast carcinoma, cancer, breast
Treatment Aromatase Inhibitor and Palbociclib
Clinical Study IdentifierNCT03439735
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Breast Cancer?
Do you have any of these conditions: cancer, breast or breast carcinoma or Breast Cancer or Breast Cancer Diagnosis?
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 nave in metastatic or locally advanced setting and planning to undergo treatment with an aromatase inhibitor (AI) and palbociclib OR receiving first-line AI 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
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