Breast CancerPhase 2NCT03439735
Determinants of Resistance to Endocrine Therapy and a Cyclin-dependent Kinases 4 and 6 (CDK4/6) Inhibitor for HR+ MBC
A Phase 2 study testing Endocrine Therapy and a CDK 4/6 inhibitor in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Endocrine Therapy and a CDK 4/6 inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2018to 1 Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read more
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Endocrine Therapy and a CDK 4/6 inhibitor
- Keywords
- Breast Cancer, Metastatic Breast Cancer, Aromatase Inhibitors, Palbociclib, Hormone Receptor Positive Metastatic Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endocrine Therapy and a CDK 4/6 inhibitorDrug
Also called ET and CDK4/6i
Participants with untreated metastatic disease receiving ET and a CDK 4/6 i as first line therapy.
Endocrine Therapy and a CDK 4/6 inhibitorDrug
Also called ET and CDK4/6i
Participants initiating a CDK 4/6 i after progression on ET.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: 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. Receives: Drug: Endocrine Therapy and a CDK 4/6 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic Mutation
The number of participants who have an ESR1 mutation prior to receiving endocrine therapy and palbociclib.
Measured: 2 years
Secondary outcomes (2)
Genetic Mutation
The amount of time from receiving palbociclib and endocrine therapy to the first detectable ESR1 mutation
Measured: 4 years
Genetic Mutation
Percentage of participants with an ESR1 mutation at the time of progression for those who received treatment with endocrine therapy and palbociclib.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start20 Jul 2018
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Safeway Foundation, Biovica International AB
- Responsible party
- Sponsor
- Investigators
- Jessica Tao, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439735
- Sponsor's protocol ID
- J17118
- Other IDs
- IRB00143030
- Status last verified
- Aug 2026
- First submitted
- 8 Dec 2017
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03439735
- Acronym / sponsor ID
- J17118
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Metastatic Breast Cancer, Aromatase Inhibitors, Palbociclib, Hormone Receptor Positive Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Safeway Foundation, Biovica International AB
- Study start
- 20 Jul 2018 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 20 Feb 2018 (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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6 | Experimental | Drug: Endocrine Therapy and a CDK 4/6 inhibitorParticipants 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. |
| Cohort B: Participants initiating a CDK 4/6 i after progression on ET. | Experimental | Drug: Endocrine Therapy and a CDK 4/6 inhibitorParticipants 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endocrine Therapy and a CDK 4/6 inhibitorAlso: ET and CDK4/6iParticipants with untreated metastatic disease receiving ET and a CDK 4/6 i as first line therapy. | Drug | Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6, Cohort B: Participants initiating a CDK 4/6 i after progression on ET. |
| Endocrine Therapy and a CDK 4/6 inhibitorAlso: ET and CDK4/6iParticipants initiating a CDK 4/6 i after progression on ET. | Drug | Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6, Cohort B: Participants initiating a CDK 4/6 i after progression on ET. |
Primary outcome
Genetic Mutation
Time frame: 2 years
The number of participants who have an ESR1 mutation prior to receiving endocrine therapy and palbociclib.
2 secondary outcomes
Genetic Mutation
Time frame: 4 years
Genetic Mutation
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- 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.
Jessica Tao, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Endocrine Therapy and a CDK 4/6 inhibitor in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
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 10 inclusion and 2 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: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetic Mutation (time frame: 2 years). 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 7 Aug 2026.