Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: SERD* + abemaciclib, SERD* + everolimus, SERD* + everolimus or capecitabine, SOC.
- Who it may be relevant to
- Registry conditions: Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-positive Breast Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE-BDT)
Overview
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.
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.
Interventions
- Drug SERD* + abemaciclib
Investigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy. - Drug SERD* + everolimus
Investigators choice Selective Estrogen Receptor Degrader + everolimus therapy. - Drug SERD* + everolimus or capecitabine
Investigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy. - Drug SOC
standard-of-care (SOC) chemotherapy in breast cancer - Drug Antiandrogen
Antiandrogen therapy
Primary outcome measures
- Intra-Individual Progression-Free Survival (PFS) [Time frame: Up to 5 years]
Secondary outcome measures (12)
- Progression free survival (PFS) - Between-Arm Evaluation [Time frame: Up to 3 months]
- Tissue- and blood-based biomarkers on response rate [Time frame: Up to 3 months]
- Overall survival (OS) [Time frame: Up to 12 months]
- Objective response rate (ORR) [Time frame: Up to 3 months]
- Duration of response (DoR) [Time frame: Up to 12 months]
- Clinical benefit rate (CBR) [Time frame: Up to 12 months]
- Grade 2 or above Adverse Events per NCI Common Terminology Criteria for Adverse Events (CTCAE) [Time frame: Up to 12 months]
- Changes in circulating tumor DNA (ctDNA) levels [Time frame: Up to 12 months]
- Changes in transcriptomic data - tissue [Time frame: Up to 12 months]
- Changes in transcriptomic data - blood [Time frame: Up to 12 months]
- Changes in Circulating tumor DNA (ctDNA) and tumor response relation [Time frame: Up to 12 months]
- Progression free survival (PFS) -Within Arm Evaluation [Time frame: Up to 5 years]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 4 centers
- Yale Cancer Center Clinical Trials Office — New Haven
- Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore
- Mayo Clinic — Rochester
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill — Chapel Hill
Identifiers
NCT: NCT07340541 · LCCC2521-TBCRC-073(EVOLVE-BDT) · 140D042590009