Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies
Purpose
This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.
Conditions
- Breast Cancer
- Metastatic Breast Cancer
- Triple Negative Breast Cancer
- Estrogen-receptor-positive Breast Cancer
- Hormone Receptor Negative Breast Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. - Subject is willing and able to comply with study procedures based on the judgement of the investigator. - Age ≥ 18 years of age at the time of consent - ECOG Performance Status of 0-2 (see APPENDIX A: ECOG Performance Status Scale). - Patients must fulfill all eligibility criteria outlined in the LCCC2521 Parent Protocol and consented to LCCC2521 Parent Protocol
Exclusion Criteria
- Inaccessible metastatic lesion to research biopsy - Subject has already initiated 2nd line therapy - Concurrent disease or condition that in the opinion of the treating oncologist renders the patient inappropriate for study participation
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Patients are stratified according to tumor marker profiles and receive corresponding treatment regimens.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Cohort 1 Arm A |
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. |
|
|
Experimental Cohort 1- Arm B |
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. |
|
|
Experimental Cohort 2 Arm A |
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. |
|
|
Experimental Cohort 2 Arm B |
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. |
|
|
Active Comparator Cohort 3 |
Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR - = Androgen Receptor negative, PD-L1 (Programmed Death-Ligand 1) positive or negative. |
|
|
Experimental Cohort 4 |
Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR + = Androgen Receptor positive, PD-L1 (Programmed Death-Ligand 1) positive or negative. |
|
Recruiting Locations
Chapel Hill, North Carolina 27599-7305
Lisa A. Carey, MD
919-966-4431
More Details
- Status
- Recruiting
- Sponsor
- UNC Lineberger Comprehensive Cancer Center
Detailed Description
The platform design makes it easy to assess multiple targeted therapies at the same time, focusing on patient groups identified by specific biomarkers. Patients who experience disease progression may be reassigned to additional eligible sub trials evaluating alternative therapeutic options. The primary endpoint for each arm is progression-free survival (PFS). This adaptive framework enables continuous learning and rapid translation of biomarker discoveries into therapeutic evaluation, promoting an agile and data-driven approach to treatment optimization in advanced breast cancer. Beyond ER and HER2, there are few biomarkers to drive treatment decisions in metastatic and primary breast cancer, leaving a gap in effective treatments for other subtypes. To address this, triple-negative (TNBC) is pioneering an adaptive, evolutionary trial focusing on women with metastatic breast cancer (MBC) in the second-line (2L) setting. The adaptive trial infrastructure is designed to serve as an integrated parent study, enabling coordinated acquisition of clinical and translational data, as well as training and testing activities. Within this framework, individual biomarker-driven sub-trials (based on biomarker development) can be created and conducted. Eligible participants include patients with ER+/HER2- or triple-negative (TNBC) metastatic breast cancer (MBC) who have progressed on first line (1L) therapy but have not yet initiated second-line (2L) treatment. HER2+ patients will be excluded due to the availability of established effective therapies. This Sub Protocol #1 will enroll subjects based on biomarker subtype. Participants will receive a standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician. In order to participate in Sub Protocol #1 subjects must have consented to the Parent protocol.