Metastatic Breast CancerENDO-RESISTNCT04579484
Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study
An observational study of Metastatic Breast Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 4 Feb 2019to 31 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Rossanna C. Pezo, MD/PhD, 416-480-4757, rossanna.pezo@sunnybrook.ca
About this study
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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Keywords
- CDK4/6 inhibitors, endocrine resistance, gut microbiome
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Identification of mutations in archival tissue samples (where available from prior testing) and sequencing of ctDNA using next generation sequencing panel
Measured: 12 months
Diversity and composition of the gut microbiome in patients with ER+ HER2- metastatic breast cancer
Analysis of the gut microbiome via 16S rRNA sequencing and metagenomic sequencing of fecal samples at baseline and at development of progressive disease
Measured: 12 months
Dietary factors and composition of the gut microbiome
Assessment of food intake via dietary questionnaire and correlation with diversity and composition of the gut microbiome
Measured: 14 days
Overall survival
Time from start of treatment until death
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start4 Feb 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rossanna C. Pezo, MD/PhD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04579484
- Sponsor's protocol ID
- ENDO-RESIST
- Acronym
- ENDO-RESIST
- Status last verified
- May 2022
- First submitted
- 1 Oct 2020
- Last updated
- 5 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study
- ClinicalTrials.gov ID
- NCT04579484
- Acronym / sponsor ID
- ENDO-RESIST / ENDO-RESIST
- Conditions
- Metastatic Breast Cancer
- Keywords
- CDK4/6 inhibitors, endocrine resistance, gut microbiome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 8 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
4 secondary outcomes
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
Diversity and composition of the gut microbiome in patients with ER+ HER2- metastatic breast cancer
Time frame: 12 months
Dietary factors and composition of the gut microbiome
Time frame: 14 days
Overall survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rossanna C. Pezo, MD/PhD principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Breast Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rossanna C. Pezo, MD/PhD (416-480-4757, rossanna.pezo@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to treatment failure (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2022.