Clinical trial NCT05933395: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Keywords: locally recurrent
metastatic
ER+
ER+/HER2-
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2023-07-06
Enrollment: 135
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

Brief 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.


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.

Primary outcomes:
measure: Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.
timeFrame: 6 - 12 months
Secondary outcomes:
measure: Incidence rate of adverse events within each treatment arm.
timeFrame: 12 months
measure: Progression-free survival within each treatment arm.
timeFrame: 12 months
measure: Rate of objective response within each treatment arm.
timeFrame: 12 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Mary Chamberlin, MD
role: PRINCIPAL_INVESTIGATOR
References: