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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
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief 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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Aromatase Inhibitor and Palbociclib Phase 2

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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Genetic Mutation [ Time Frame: 2 years ]
    The number of participants who have an ESR1 mutation prior to receiving an aromatase inhibitor and palbociclib.


Secondary Outcome Measures :
  1. Genetic Mutation [ Time Frame: 4 years ]
    The amount of time from receiving palbociclib and aromatase inhibitor to the first detectable ESR1 mutation

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Hopkins Breast Trials 410-614-1361 hopkinsbreasttrials@jhmi.edu
Contact: Sidney Kimmel Comprehensive Cancer Centers Clinical Research Office 410-955-8866 jhcccro@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Hopkins Breast Trials    410-614-1361    hopkinsbreasttrials@jhmi.edu   
Contact: Johns Hopkins Clinical Research Office    410-955-8866    JHCCCRO@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
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Principal Investigator: Maria Nunes, M.D. Sibley Memorial Hospital

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03439735     History of Changes
Other Study ID Numbers: J17118
IRB00143030 ( Other Identifier: JHM-IRB )
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Breast Cancer
Metastatic Breast Cancer
Aromatase Inhibitors
Palbociclib
Hormone Receptor Positive Metastatic Breast Cancer
Additional relevant MeSH terms:
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Estrogen Antagonists
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Palbociclib
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists