Genetically-informed Therapy for ER+ Breast Cancer in a Post-CDK4/6 Inhibitor Setting: a Phase II Umbrella Study (GERTRUDE)

Dartmouth-Hitchcock Medical Center1 个研究点分布在 1 个国家目标入组 135 人开始时间: 2024年9月23日最近更新: 2026年1月20日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方: Dartmouth-Hitchcock Medical Center
入组人数: 135
试验地点: 1
主要终点: Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to learn if certain drug combinations are effective treatments for patients with advanced ER+/HER2- who have previously been treated with palbociclib, ribociclib, or abemaciclib.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Diagnostic
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

•Post-menopausal women ≥18 years of age with metastatic ER+ breast cancer, or with locally recurrent ER+ disease not amenable to therapy for curative intent.
•Patient must be post-menopausal per NCCN guidelines.
•Patient must have been treated with a CDK4/6i (either palbobclib, ribociclib, or abemaciclib) alone or in combination with an endocrine agent in the advanced disease setting.
•Up to 3 lines of therapy following CDK4/6i are permissible.
•Any number of prior lines of endocrine-containing therapy is permissible.
•Up to 1 prior line of chemotherapy is permissible.
•Histologic documentation of ER+ breast cancer by core needle biopsy, fine needle aspiration, incisional biopsy, or surgical biopsy of ≥1 site(s) of metastatic or locally recurrent disease performed as standard of care.
•Exceptions: patients with bone-dominant metastatic disease, or non-bone metastatic disease in whom a safe and accurate biopsy of recurrent/metastatic disease cannot be readily obtained, with a history of ER+ breast cancer are eligible, and biopsy is not required, providing their primary cancer is consistent with the ER criteria described below.
•ER+ status defined as ER staining by immunohistochemistry in ≥1% of malignant cell nuclei.
•Tumor must be HER2-non-amplified as defined by an immunohistochemistry score of 0-1+, or with a FISH ratio <2 if IHC is 2+ or if IHC has not been done (as per ASCO/CAP definitions). In cases of borderline or equivocal HER2 status, eligibility will be determined by the PI.
•Genetic profiling of a tumor or plasma specimen acquired after disease progression on a CDK4/6i must have been performed in a CAP-accredited, CLIA-certified laboratory using clinically validated methods. Profiling must minimally include analysis of study-relevant alterations in ERBB2, PIK3CA, AKT1, MTOR, PTEN, and RB
•If not done: Profiling of a tumor (preferable) or plasma specimen will be performed as part of the study in the DHMC Pathology Laboratory. A plasma specimen may be obtained for study-specific genetic profiling to direct treatment assignment. Tumor specimens must be obtained outside of this study (e.g., by biopsy).
•If available, archived tumor tissue must be accessible for research purposes, sufficient to make ≥10 five-micron sections; more tumor tissue is preferred.
•Radiographic staging performed as standard of care, including specifically either PET/CT, or contrast CT (CAP) and bone scan.
•Patient must be capable and willing to provide informed written consent for study participation.

排除标准

•Treatment with abemaciclib in the most recent or current line of therapy.
•During the study Treatment Phases, no concurrent anti-cancer therapies are allowed with the following exception: anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
•Any investigational cancer therapy in the last 3 weeks.
•Known untreated CNS disease, unless clinically stable for ≥ 3 months.

研究组 & 干预措施

Arm A- neratinib and fulvestrant

Experimental

Participants with a qualifying ERBB2 (HER2) mutation will be assigned to Treatment Arm A and given the combination of neratinib and fulvestrant until the end of the primary treatment phase.