Breast CancerPhase 2AIM-BRIGHTNCT07227233
Artificial Intelligence and Machine Learning to Guide CDK4/6 Inhibitor Rechallenge in Breast Cancer.
A Phase 2 study testing A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. and Treatment of physician's choice in people with Breast Cancer, run by University of California, San Diego at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if an artificial intelligence model will be able to select patients with advanced breast cancer who may respond to a second cyclin-dependent kinase 4/6 (CDK4/6) inhibitor after they have progressed on the first CDK4/6 inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. and Treatment of physician's choice
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2026to Dec 2028
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- Eastern Cooperative Oncology Group performance status 0-2
- Ability to understand and sign the informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Advanced breast cancer (defined as unresectable or metastatic) histologically confirmed hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer per American Society of Clinical Oncology/College of American Pathologists (CAP) guidelines.
- Endocrine-sensitive disease per the 7th International Consensus Conference on Advanced Breast Cancer (ABC7) 2023 guideline: no relapse during the first 2 years of adjuvant endocrine therapy or progression within the first 6 months of first-line endocrine therapy in the metastatic setting.
Show all 29Show fewer
- Progression of disease, radiographically per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria or clinically per physician assessment, after a minimum of 6 months of 1 prior line of any CDK4/6 inhibitor therapy plus or minus endocrine therapy in the metastatic setting, or within 6 months of completing adjuvant CDK4/6 inhibitor with endocrine therapy.
- An additional line of therapy with CDK4/6i is possible and available.
- Zero to 1 prior line of chemotherapy or antibody-drug conjugates in the metastatic setting.
- Available next-generation sequencing panel testing results - or possibility to perform next-generation sequencing panel testing - on tumor tissue biopsy collected within 6 months of enrollment but after CDK4/6 inhibitor exposure. Note that If biopsy was performed more than 6 months before enrollment, the patient is not eligible to participate, unless the biopsy is repeated during the prescreening phase. Adequate tissue/testing will be one of these:
- safe non-osseous tumor site for fresh tissue biopsy and subsequent tissue-based next-generation sequencing testing by any Clinical Laboratory Improvement-certified laboratory. Biopsy and next-generation sequencing testing will be performed as standard of care evaluation.
- archival non-osseous tumor tissue adequate for standard of care next-generation sequencing testing by any Clinical Laboratory Improvement Amendments-certified labs.
- prior tissue-based next-generation sequencing testing on tissue that was collected and performed within 6 months of study enrollment.
- Palbociclib sensitive disease as determined by the palbo-VNN model.
- Participants can have non-measurable but evaluable disease or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Participants must have organ and marrow function as defined below:
- Leukocytes > 3,000/microliter
- Hemoglobin > 8 g/deciliter
- Absolute neutrophil count > 1,200/microliter
- Platelets > 75,000/microliter
- For participants of reproductive potential:
- Females: use of highly effective contraception for at least 1 month before initiation of treatment with study medications (cycle 1 day 1) and agreement to use such a method during study participation and until 3 months after the end of treatment visit. Only non-hormonal contraception (eg., copper intrauterine device, barrier, condoms with spermicidal, sponge with spermicidal, or diaphragm with spermicidal), is allowed.
- Males: use of condoms or other methods to ensure effective contraception with a partner during study participation and until 3 months after the end of treatment visit. For partners, use of hormonal contraception is allowed.
- Palliative radiotherapy is allowed.
- Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate locoregional central nervous system-specific treatment is not required and is unlikely to be required during the first cycle of therapy.
- Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
- For participants with evidence of chronic hepatitis B virus infection, the viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus infection must have been treated and cured. For participants with hepatitis C virus infection who are currently on treatment, they are eligible if they have an undetectable viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible.
Who cannot join
- Life expectancy less than 6 months.
- Any medical or psychiatric condition that would prevent the safe use of a CDK4/6 inhibitor or fulvestrant or treatment of physician's choice or the ability to participate in study procedures.
- Participants who are receiving any other investigational agents within 3 weeks of study enrollment only if there is a known pharmacokinetic interaction with the selected drug. No washout period is otherwise required.
- Uncontrolled intercurrent illness including ongoing or active infection, congestive heart failure, unstable angina pectoris or cardiac arrhythmia, lung disease requiring continuous oxygen supplementation, decompensated cirrhosis, end-stage kidney disease on dialysis, or psychiatric illness that limits the ability to participate in the study.
- Unable to have access to abemaciclib, palbociclib, ribociclib, or fulvestrant as a standard of care treatment.
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Diego
La Jolla, California, 92093
Kay Yeung, MD, PhD, 858-822-5354, CancerCTO@health.ucsd.edu
Breast Research Team, 858-822-5354, CancerCTO@health.ucsd.edu
About this study
Official title: Artificial Intelligence and Machine Learning-Enhanced Biomarker-dRiven CDK4/6 Inhibitor Rechallenge in HR+ HER2- Advanced Breast Tumors.
The goal of this clinical trial is to learn if an artificial intelligence model will be able to select patients with advanced breast cancer who may respond to a second cyclin-dependent kinase 4/6 (CDK4/6) inhibitor after they have progressed on the first CDK4/6 inhibitor. Patients for this study need to have hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.
The main questions the study aims to answer are:
Read more
If the artificial intelligence model says that a patient's tumor should respond to the second CDK4/6 inhibitor, and that patient receives the second CDK4/6 inhibitor together with fulvestrant (an endocrine therapy also called Faslodex), will it take longer for the tumor to get worse than if the patient receives another type of therapy? Will the tumor respond better? Will the therapy be safe?
Researchers will compare the combination of a second CDK4/6 inhibitor plus fulvestrant to the therapy chosen by the physician.
Participants will:
Take the assigned therapy based on the way the therapy is usually prescribed. Visit the clinic once every month for checkups, tests, and questionnaires. Keep a diary of the pills they take at home.
Read the detailed description
This is a phase II, open-label, randomized controlled single-site study to assess the clinical utility of an artificial intelligence model, called palbo-VNN, to guide treatment selection in patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced (unresectable or metastatic) breast cancer who have progressed after prior treatment with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The investigators hypothesize that: (1) the model will be able to predict who will respond to a second CDK4/6 inhibitors combined with fulvestrant (Faslodex); and (2) that the participants treated with a second CDK4/6 inhibitors plus fulvestrant will have better outcomes (longer progression free survival, higher overall response rate, higher clinical benefit rate, and better quality of life) than the participants treated based on the physician's choice.
Next-generation sequencing of the tumor will be performed using biopsies obtained after the first CDK4/6 inhibitor treatment and within six months of study enrollment. The next-generation sequencing data will be analyzed with the palbo-VNN model. Participants with tumors predicted to respond to a second CDK4/6 inhibitor (CDK4/6i sensitive) will be randomized. Half of the randomized participants will receive a second CDK4/6 inhibitor plus fulvestrant; the other half will receive the treatment of physician's choice, excluding CDK4/6 inhibitors.
After 6 months of therapy, the investigators will evaluate the progression free survival rate of the randomized participants, as well as other measures of efficacy, such as overall response rate, clinical benefit rate, and quality of life. They will also do studies to correlate treatment efficacy with molecular alterations of the tumor. These correlative studies may allow to improve the predictive ability of the palbo-VNN model in the future. The investigators will also evaluate treatment safety.
- Conditions
- Breast Cancer
- Being tested
- A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant., Treatment of physician's choice
- Keywords
- Unresectable breast cancer, Metastatic breast cancer, Cyclin-dependent kinase 4/6 inhibitors, Artificial intelligence model, Human epidermal growth factor receptor 2 negative (HER2- ), Hormone receptor positive (HR+), Fulvestrant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant.Drug
A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant.
Treatment of physician's choiceDrug
Treatment of physician's choice, excluding CDK4/6 inhibitors.
| Study group | Role | What they receive |
|---|---|---|
| Second CDK4/6 inhibitor plus fulvestrant | Experimental | A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. Receives: Drug: A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. |
| Treatment of physician's choice | Active comparator | Treatment of physician's choice, excluding CDK4/6 inhibitors. Receives: Drug: Treatment of physician's choice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Rate of progression free survival at 6 months after randomization.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2025
- Study start31 Mar 2026
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kay Yeung, University of California, San Diego
- Investigators
- Kay Yeung, MD, PhD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07227233
- Sponsor's protocol ID
- 812480
- Acronym
- AIM-BRIGHT
- Status last verified
- Apr 2026
- First submitted
- 10 Nov 2025
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Park S, Silva E, Singhal A, Kelly MR, Licon K, Panagiotou I, Fogg C, Fong S, Lee JJY, Zhao X, Bachelder R, Parker BA, Yeung KT, Ideker T. A deep learning model of tumor cell architecture elucidates response and resistance to CDK4/6 inhibitors. Nat Cancer. 2024 Jul;5(7):996-1009. doi: 10.1038/s43018-024-00740-1. Epub 2024 Mar 5.
PubMed 38443662
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Artificial Intelligence and Machine Learning-Enhanced Biomarker-dRiven CDK4/6 Inhibitor Rechallenge in HR+ HER2- Advanced Breast Tumors.
- ClinicalTrials.gov ID
- NCT07227233
- Acronym / sponsor ID
- AIM-BRIGHT / 812480
- Conditions
- Breast Cancer
- Keywords
- Unresectable breast cancer, Metastatic breast cancer, Cyclin-dependent kinase 4/6 inhibitors, Artificial intelligence model, Human epidermal growth factor receptor 2 negative (HER2- ), Hormone receptor positive (HR+), Fulvestrant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 31 Mar 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 12 Nov 2025 (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 clinical trial is to learn if an artificial intelligence model will be able to select patients with advanced breast cancer who may respond to a second cyclin-dependent kinase 4/6 (CDK4/6) inhibitor after they have progressed on the first CDK4/6 inhibitor. Patients for this study need to have hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.
The main questions the study aims to answer are:
If the artificial intelligence model says that a patient's tumor should respond to the second CDK4/6 inhibitor, and that patient receives the second CDK4/6 inhibitor together with fulvestrant (an endocrine therapy also called Faslodex), will it take longer for the tumor to get worse than if the patient receives another type of therapy? Will the tumor respond better? Will the therapy be safe?
Researchers will compare the combination of a second CDK4/6 inhibitor plus fulvestrant to the therapy chosen by the physician.
Participants will:
Take the assigned therapy based on the way the therapy is usually prescribed. Visit the clinic once every month for checkups, tests, and questionnaires. Keep a diary of the pills they take at home.
Detailed description
This is a phase II, open-label, randomized controlled single-site study to assess the clinical utility of an artificial intelligence model, called palbo-VNN, to guide treatment selection in patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced (unresectable or metastatic) breast cancer who have progressed after prior treatment with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The investigators hypothesize that: (1) the model will be able to predict who will respond to a second CDK4/6 inhibitors combined with fulvestrant (Faslodex); and (2) that the participants treated with a second CDK4/6 inhibitors plus fulvestrant will have better outcomes (longer progression free survival, higher overall response rate, higher clinical benefit rate, and better quality of life) than the participants treated based on the physician's choice.
Next-generation sequencing of the tumor will be performed using biopsies obtained after the first CDK4/6 inhibitor treatment and within six months of study enrollment. The next-generation sequencing data will be analyzed with the palbo-VNN model. Participants with tumors predicted to respond to a second CDK4/6 inhibitor (CDK4/6i sensitive) will be randomized. Half of the randomized participants will receive a second CDK4/6 inhibitor plus fulvestrant; the other half will receive the treatment of physician's choice, excluding CDK4/6 inhibitors.
After 6 months of therapy, the investigators will evaluate the progression free survival rate of the randomized participants, as well as other measures of efficacy, such as overall response rate, clinical benefit rate, and quality of life. They will also do studies to correlate treatment efficacy with molecular alterations of the tumor. These correlative studies may allow to improve the predictive ability of the palbo-VNN model in the future. The investigators will also evaluate treatment safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Second CDK4/6 inhibitor plus fulvestrant | Experimental | Drug: A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant.A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. |
| Treatment of physician's choice | Active comparator | Drug: Treatment of physician's choiceTreatment of physician's choice, excluding CDK4/6 inhibitors. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Age >18 years
- Eastern Cooperative Oncology Group performance status 0-2
- Ability to understand and sign the informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Advanced breast cancer (defined as unresectable or metastatic) histologically confirmed hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer per American Society of Clinical Oncology/College of American Pathologists (CAP) guidelines.
Key exclusion criteria (6 listed)
- Life expectancy less than 6 months.
- Any medical or psychiatric condition that would prevent the safe use of a CDK4/6 inhibitor or fulvestrant or treatment of physician's choice or the ability to participate in study procedures.
- Participants who are receiving any other investigational agents within 3 weeks of study enrollment only if there is a known pharmacokinetic interaction with the selected drug. No washout period is otherwise required.
- Uncontrolled intercurrent illness including ongoing or active infection, congestive heart failure, unstable angina pectoris or cardiac arrhythmia, lung disease requiring continuous oxygen supplementation, decompensated cirrhosis, end-stage kidney disease on dialysis, or psychiatric illness that limits the ability to participate in the study.
- Unable to have access to abemaciclib, palbociclib, ribociclib, or fulvestrant as a standard of care treatment.
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 |
|---|---|---|
| A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant.A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. | Drug | Second CDK4/6 inhibitor plus fulvestrant |
| Treatment of physician's choiceTreatment of physician's choice, excluding CDK4/6 inhibitors. | Drug | Treatment of physician's choice |
Primary outcome
Progression free survival
Time frame: 6 months
Rate of progression free survival at 6 months after randomization.
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 9 Apr 2026.
- Background: PubMed 38443662Park S, Silva E, Singhal A, Kelly MR, Licon K, Panagiotou I, Fogg C, Fong S, Lee JJY, Zhao X, Bachelder R, Parker BA, Yeung KT, Ideker T. A deep learning model of tumor cell architecture elucidates response and resistance to CDK4/6 inhibitors. Nat Cancer. 2024 Jul;5(7):996-1009. doi: 10.1038/s43018-024-00740-1. Epub 2024 Mar 5.
- PubMedLink provided by the sponsor.
- 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.
Kay Yeung, MD, PhD principal investigator
University of California, San Diego
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 A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant. and Treatment of physician's choice in people with Breast Cancer, run by University of California, San Diego 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 29 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 9 Apr 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?
Contact Kay Yeung, MD, PhD (858-822-5354, CancerCTO@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07227233, which also lists 1 linked publication.
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 9 Apr 2026.