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Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study (ENDO-RESIST)

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ClinicalTrials.gov Identifier: NCT04579484
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Study Description
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Brief Summary:
This is a single-center prospective study involving analysis of circulating tumor DNA (ctDNA) and the gut microbiome in patients with metastatic breast cancer on standard of care endocrine therapy with an aromatase inhibitor in combination with an inhibitor of the cyclin-dependent kinases 4 and 6 (CDK 4/6). Up to 20 patients with Estrogen Receptor positive (ER+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0-1 will be enrolled. This study involves the collection and analysis of patient samples and does not involve therapeutic intervention.

Condition or disease
Metastatic Breast Cancer

Detailed Description:

Endocrine therapies have been associated with an overall survival benefit in breast cancer and are the preferred initial treatment approach in patients with ER+, HER2- metastatic breast cancer. Unfortunately, resistance to endocrine therapies eventually develops in the metastatic setting and metastatic breast cancer remains an incurable disease. Endocrine resistance may develop as a result of alterations in estrogen signaling and metabolism pathways, which may be modulated by gut bacteria. In addition, genomic profiling of archival tissues and circulating tumor DNA (ctDNA) in ER+ breast cancer has identified multiple somatic molecular alterations that may mediate response to endocrine therapies.

This study is designed to identify markers of endocrine resistance in ctDNA and the gut microbiome in patients with ER+ HER2- metastatic breast cancer.

Study Design
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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study
Actual Study Start Date : February 4, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Time to treatment failure [ Time Frame: 12 months ]
    Time from first treatment on study (standard of care aromatase inhibitor and a CDK 4/6 inhibitor) until the date of treatment discontinuation


Secondary Outcome Measures :
  1. Correlation between specific mutations in ctDNA and in archival tissue samples (where available from prior testing) with time to treatment failure [ Time Frame: 12 months ]
    Identification of mutations in archival tissue samples (where available from prior testing) and sequencing of ctDNA using next generation sequencing panel

  2. Diversity and composition of the gut microbiome in patients with ER+ HER2- metastatic breast cancer [ Time Frame: 12 months ]
    Analysis of the gut microbiome via 16S rRNA sequencing and metagenomic sequencing of fecal samples at baseline and at development of progressive disease

  3. Dietary factors and composition of the gut microbiome [ Time Frame: 14 days ]
    Assessment of food intake via dietary questionnaire and correlation with diversity and composition of the gut microbiome

  4. Overall survival [ Time Frame: 2 years ]
    Time from start of treatment until death


Biospecimen Retention:   Samples With DNA
Peripheral blood samples and fecal samples will be collected at baseline, after 1 month on treatment and on change in treatment due to disease progression. Sampling will coincide with clinic visits.

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Patients with ER positive and HER2 negative metastatic breast cancer planned to initiate on standard of care treatment with an aromatase inhibitor and a CDK 4/6 inhibitor
Criteria

Inclusion Criteria:

  • Sign written and voluntary informed consent
  • Histological confirmation of advanced ER positive and HER2 negative breast cancer.
  • Adult patients at least 18 years of age
  • ECOG performance status equal to 0 or 1
  • Able to provide written informed consent
  • Must be willing to provide blood for ctDNA analysis on study enrollment and at specified study time points
  • Must be willing and able to perform stool sample collection
  • Patients must be suitable, as per their treating physician, for initiation of first line endocrine therapy with an aromatase inhibitor and a CDK 4/6 inhibitor for metastatic disease

Exclusion Criteria:

  • Prior treatment with CDK 4/6 inhibitors in the neoadjuvant or adjuvant setting
  • Use of targeted therapies other than endocrine therapies alone in the neoadjuvant or adjuvant setting
  • Relapse on prior endocrine therapy or within 6 months of discontinuation of prior adjuvant endocrine therapy
  • History of inflammatory bowel disease, chronic diarrhea or malabsorption syndromes and significant prior bowel resection as judged by the study investigator
  • Use of immunosuppressants including steroids within the previous 4 weeks of planned Cycle 1 Day 1 treatment
Contacts and Locations
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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): NCT04579484


Contacts
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Contact: Rossanna C. Pezo, MD/PhD 416-480-4757 rossanna.pezo@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Rossanna C. Pezo, MD/PhD    416-480-4757    rossanna.pezo@sunnybrook.ca   
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
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Principal Investigator: Rossanna C. Pezo, MD/PhD Sunnybrook Health Sciences Centre
More Information
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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04579484    
Other Study ID Numbers: ENDO-RESIST
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sunnybrook Health Sciences Centre:
endocrine therapies
enodcrine resistance
gut microbiome
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases