Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study

NCT04579484 | Unknown

• 1 other identifier: ENDO-RESIST
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Keywords

CDK4/6 inhibitors; endocrine resistance; gut microbiome

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure

  Time from first treatment on study (standard of care aromatase inhibitor and a CDK 4/6 inhibitor) until the date of treatment discontinuation

  12 months

Secondary Outcomes (4)

• Correlation between specific mutations in ctDNA and in archival tissue samples (where available from prior testing) with time to treatment failure

  12 months

• Diversity and composition of the gut microbiome in patients with ER+ HER2- metastatic breast cancer

  12 months

• Dietary factors and composition of the gut microbiome

  14 days

• Overall survival

  2 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

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.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Rossanna C. Pezo, MD/PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rossanna C. Pezo, MD/PhD

CONTACT

416-480-4757; rossanna.pezo@sunnybrook.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: February 4, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 5, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)