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

Advanced Breast Cancer Clinical Trial

— GERTRUDE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05933395
• Other study ID #: STUDY02001800
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2023
• Est. completion date: October 2031

Study information

• Verified date: October 2023
• Source: Dartmouth-Hitchcock Medical Center
• Contact: Research Nurse
• Phone: 603-650-5021
• Email: hem-onc.research.nurses[@]hitchcock.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: October 2031
• Est. primary completion date: October 2030
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.	Clinical benefit rate will be measured as the proportion of participants who experience stable disease (SD) at 24 weeks, complete response, and partial response per RECIST 1.1.	6 - 12 months
Secondary	Incidence rate of adverse events within each treatment arm.	Number of participants with treatment-related adverse events as assessed by CTCAE within each treatment arm.	12 months
Secondary	Progression-free survival within each treatment arm.	Progression-free survival will be measured by the time between the initiation of study treatment to the time of progression per RECIST 1.1.	12 months
Secondary	Rate of objective response within each treatment arm.	The proportion of participants within each arm who experience objective response defined as complete or partial response per RECIST 1.1 while on study treatment will be measured.	12 months