Clinical Trial: NCT03439735 - My Cancer Genome

NCT03439735

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.

Related Conditions:

Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03439735

Trial Eligibility

Document

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

Breast Cancer

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

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

Clinical Trials /

Determinants of Resistance to Endocrine Therapy and a Cyclin-dependent Kinases 4 and 6 (CDK4/6) Inhibitor for HR+ MBC