Clinical Trials /

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

NCT03439735

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: J17118
  • SECONDARY ID: IRB00143030
  • NCT ID: NCT03439735

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Aromatase Inhibitor and PalbociclibAI and palboPalbociclib and Aromatase Inhibitor

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib and Aromatase InhibitorExperimentalParticipants 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.
  • Aromatase Inhibitor and Palbociclib

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 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.
      
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 an aromatase inhibitor and palbociclib.

Secondary Outcome Measures

Measure:Genetic Mutation
Time Frame:4 years
Safety Issue:
Description:The amount of time from receiving palbociclib and aromatase inhibitor 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 an aromatase inhibitor 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

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