Artificial Intelligence and Machine Learning to Guide CDK4/6 Inhibitor Rechallenge in Breast Cancer.

NCT07227233 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 812480
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Rate of progression free survival at 6 months after randomization.

  6 months

Study Arms (2)

Second CDK4/6 inhibitor plus fulvestrant

EXPERIMENTAL

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 choice

ACTIVE COMPARATOR

Treatment of physician's choice, excluding CDK4/6 inhibitors.

Drug: Treatment of physician's choice

Interventions

Treatment of physician's choice DRUG

Treatment of physician's choice, excluding CDK4/6 inhibitors.

Treatment of physician's choice

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.

Second CDK4/6 inhibitor plus fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 38443662 BACKGROUND

Related Links

• PubMed

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Kay Yeung, MD, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kay Yeung, MD, PhD

CONTACT

858-822-5354; CancerCTO@health.ucsd.edu

Breast Research Team

CONTACT

858-822-5354; cancerCTO@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 12, 2025
• Study Start: March 31, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)