Determinants of Resistance to First-line Therapy With an AI and Palbociclib for HR+ MBC
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|ClinicalTrials.gov Identifier: NCT03439735|
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : August 29, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Aromatase Inhibitor and Palbociclib||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 20, 2018|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||July 1, 2022|
Experimental: Palbociclib and Aromatase Inhibitor
Participants will undergo blood collection (intervention) at time of initiating treatment with an aromatase inhibitor 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: Aromatase Inhibitor and Palbociclib
Participants that are initiating treatment with an AI and Palbociclib.
Other Name: AI and palbo
- Genetic Mutation [ Time Frame: 2 years ]The number of participants who have an ESR1 mutation prior to receiving an aromatase inhibitor and palbociclib.
- Genetic Mutation [ Time Frame: 4 years ]The amount of time from receiving palbociclib and aromatase inhibitor to the first detectable ESR1 mutation
- Genetic Mutation [ Time Frame: 3 years ]Percentage of participants with an ESR1 mutation at the time of progression for those who received treatment with an aromatase inhibitor and palbociclib.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439735
|Contact: Hopkins Breast Trialsfirstname.lastname@example.org|
|Contact: Sidney Kimmel Comprehensive Cancer Centers Clinical Research Officeemail@example.com|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Hopkins Breast Trials 410-614-1361 firstname.lastname@example.org|
|Contact: Johns Hopkins Clinical Research Office 410-955-8866 JHCCCRO@jhmi.edu|
|Principal Investigator:||Maria Nunes, M.D.||Sibley Memorial Hospital|