Description:
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.
Title
- Brief Title: Determinants of Resistance to Endocrine Therapy and a Cyclin-dependent Kinases 4 and 6 (CDK4/6) Inhibitor for HR+ MBC
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
J17118
- SECONDARY ID:
IRB00143030
- NCT ID:
NCT03439735
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Endocrine Therapy and a CDK 4/6 inhibitor | ET and CDK4/6i | Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6 |
Endocrine Therapy and a CDK 4/6 inhibitor | ET and CDK4/6i | Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6 |
Purpose
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
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Endocrine Therapy and a CDK 4/6 inhibitor
- 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. | - Endocrine Therapy and a CDK 4/6 inhibitor
- Endocrine Therapy and a CDK 4/6 inhibitor
|
Eligibility 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.
Maximum Eligible Age: | 100 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Genetic Mutation |
Time Frame: | 2 years |
Safety Issue: | |
Description: | The number of participants who have an ESR1 mutation prior to receiving endocrine therapy and palbociclib. |
Secondary Outcome Measures
Measure: | Genetic Mutation |
Time Frame: | 4 years |
Safety Issue: | |
Description: | The amount of time from receiving palbociclib and endocrine therapy to the first detectable ESR1 mutation |
Measure: | Genetic Mutation |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Percentage of participants with an ESR1 mutation at the time of progression for those who received treatment with endocrine therapy and palbociclib. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- Breast Cancer
- Metastatic Breast Cancer
- Aromatase Inhibitors
- Palbociclib
- Hormone Receptor Positive Metastatic Breast Cancer
Last Updated
July 13, 2021