Determinants of Resistance to First-line Therapy With an AI and Palbociclib for HR+ MBC
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 8/17/2018 |
| Start Date: | July 20, 2018 |
| End Date: | July 1, 2022 |
| Contact: | Hopkins Breast Trials |
| Email: | hopkinsbreasttrials@jhmi.edu |
| Phone: | 410-614-1361 |
Prospective Evaluation of Determinants of Resistance to First-line Therapy With an Aromatase Inhibitor and the Cyclin-dependent Kinases 4 and 6 Inhibitor Palbociclib in Hormone Receptor Positive Metastatic Breast Cancer
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.
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.
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 naïve
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.
progesterone receptor (ER/ PR) positive metastatic breast cancer (MBC). Data regarding
primary resistance and patterns of emergence of acquired resistance in treatment naïve
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.
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 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.
We found this trial at
1
site
3400 N Charles St
Baltimore, Maryland 21205
Baltimore, Maryland 21205
410-516-8000
Phone: 410-614-1361
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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