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

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

NCT ID: NCT05933395

Condition: Advanced Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Everolimus
Fulvestrant
Neratinib

Conditions: Keywords:
locally recurrent
metastatic
ER+
ER+/HER2-

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: This study has a non-randomized umbrella design. Participants will be assigned to a treatment arm based on tumor/plasma genetic profiling and treatment history using the primary treatment phase algorithm.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Fulvestrant
Description: Fulvestrant will be administered intramuscularly into the buttocks in combination with one of the other interventions as outlined above.
Arm group label: Arm A- neratinib and fulvestrant
Arm group label: Arm B- alpelisib and fulvestrant
Arm group label: Arm C- everolimus and fulvestrant
Arm group label: Arm D- abemaciclib and fulvestrant

Intervention type: Drug
Intervention name: Neratinib
Description: Neratinib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
Arm group label: Arm A- neratinib and fulvestrant

Intervention type: Drug
Intervention name: Alpelisib
Description: Alpelisib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
Arm group label: Arm B- alpelisib and fulvestrant

Intervention type: Drug
Intervention name: Everolimus
Description: Everolimus will be administered orally in tablet form once daily in combination with fulvestrant administration as outlined above.
Arm group label: Arm C- everolimus and fulvestrant

Intervention type: Drug
Intervention name: Abemaciclib
Description: Abemaciclib will be administered orally in tablet form twice daily in combination with fulvestrant administration as outlined above.
Arm group label: Arm D- abemaciclib and fulvestrant

Summary: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. 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. 2. Patient must be post-menopausal per NCCN guidelines. 3. 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. 4. 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. 5. ER+ status defined as ER staining by immunohistochemistry in ≥1% of malignant cell nuclei. 6. 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. 7. 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). 8. If available, archived tumor tissue must be accessible for research purposes, sufficient to make ≥10 five-micron sections; more tumor tissue is preferred. 9. Radiographic staging performed as standard of care, including specifically either PET/CT, or contrast CT (CAP) and bone scan. 10. Patient must be capable and willing to provide informed written consent for study participation. Exclusion Criteria: 1. Treatment with abemaciclib in the most recent or current line of therapy. 2. 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. 3. Any investigational cancer therapy in the last 3 weeks. 4. Known untreated CNS disease, unless clinically stable for ≥ 3 months.

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Dartmouth Hitchcock Medical Center

Address:
City: Lebanon
Zip: 03756
Country: United States

Status: Recruiting

Contact:
Last name: Research Nurse

Phone: 603-650-5021
Email: hem-onc.research.nurses@hitchcock.org

Contact backup:
Last name: Rachel Wierzbicki

Phone: 6036505021

Start date: October 10, 2023

Completion date: October 2031

Lead sponsor:
Agency: Dartmouth-Hitchcock Medical Center
Agency class: Other

Source: Dartmouth-Hitchcock Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05933395