Genetically-informed Therapy for ER+ Breast Cancer Post-CDK4/6 Inhibitor

Official title

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

Overview

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.

Interventions

• Drug Fulvestrant
  Fulvestrant will be administered intramuscularly into the buttocks in combination with one of the other interventions as outlined above.
• Drug Neratinib
  Neratinib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
• Drug Alpelisib
  Alpelisib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
• Drug Everolimus
  Everolimus will be administered orally in tablet form once daily in combination with fulvestrant administration as outlined above.
• Drug Abemaciclib
  Abemaciclib will be administered orally in tablet form twice daily in combination with fulvestrant administration as outlined above.

Primary outcome measures

• Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor. [Time frame: 6 - 12 months]

Secondary outcome measures (3)

• Incidence rate of adverse events within each treatment arm. [Time frame: 12 months]
• Progression-free survival within each treatment arm. [Time frame: 12 months]
• Rate of objective response within each treatment arm. [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• 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 RB1.

• 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.

Exclusion criteria

• 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.

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

Diagnostic

Study locations

United States · 1 center

• Dartmouth Hitchcock Medical Center — Lebanon

Identifiers

NCT: NCT05933395 · STUDY02001800 · NCI-2024-09317

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗