Clinical trial NCT05101564: Umbrella Trial Testing Integrative Subtype Targeted Therapeutics in Estrogen Receptor Positive, HER2-Negative Breast Cancer
Official title: An Umbrella, Randomized, Controlled, Pre Operative Trial Testing Integrative Subtype Targeted Therapeutics in Estrogen Receptor Positive, HER2-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
HER2-negative Breast Cancer
ER Positive Breast Cancer
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2021-11-01
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn if adding a new drug that is targeted at a specific genetic change found in some breast tumors pre-operatively will slow the growth of the tumor more than standard anti-hormone therapy used to treat this type of breast cancer. Different therapies are being tested based on the specific gene changes in the tumor. Not every tumor will have a gene change that is being studied.

Detailed description: Primary Objective: To evaluate the efficacy of investigational agent compared with standard endocrine therapy in in reducing Ki67 values based on digital pathology (QuPath) from baseline to on-treatment biopsy after an specific treatment duration (i.e. 14 days) in ER-positive, HER2-negative tumors (tumor size ≥1 cm) with Ki67 ≥ 10%, for different integrative subtype categories identified at integrative subtype screening.

Secondary Objective: To evaluate the efficacy of investigational agent compared with standard endocrine therapy on the proportion of subjects with Ki67 \< 10% after a specific treatment duration (i.e. 14 days)

Eligibility criteria: Inclusion Criteria:

* Pre-Screening Phase
* Biopsy-proven ER-positive, HER2-negative breast cancer. ER-positivity and PR-positivity are defined as ≥1% cells staining positive by immunohistochemistry. HER2-negativity is defined by IHC or FISH, per ASCO-CAP 2018 guidelines. Breast tumor must be intact and tumor size must be ≥ 1 cm as measured by ultrasound, mammogram, MRI, or clinical exam. If tumor is locally recurrent, it must be in the breast (not skin, node, or chest wall recurrence). Ki67 may or may not have been done locally but if done locally, must be ≥ 5%. Any nodal status is allowed, as M0 or M1 disease.
* Women or men, age ≥ 18 years old.
* Performance status 0 to 1 (by Eastern Cooperative Oncology Group \[ECOG\] scale).
* Ability to understand and the willingness to sign a written informed consent document.

Treatment Phase

* Breast tumor classifies as relevant integrative subtype per tumor sequencing performed and analyzed by central laboratory.
* Breast tumor Ki67 score ≥ 10% as assessed by central laboratory.
* Each investigational agent specific inclusion criteria can be found in the agent-specific appendix

Exclusion Criteria:

* Pregnant woman, as confirmed by positive serum hCG test prior to initiating study treatment. Nursing (lactating) woman also not allowed.
* Prior breast cancer-directed therapy (surgery, radiation, chemotherapy, or endocrine therapy) is not allowed, with the exception of people with in-breast recurrences. People with in-breast recurrences cannot have had breast cancer-directed therapy (radiation, chemotherapy, or endocrine therapy; surgery is acceptable) within the 6 months prior to signing the pre-screening consent. Pre-endocrine therapy for breast cancer risk reduction is allowed.
* Known hypersensitivity to study agent (IP) or standard endocrine therapy drug, or to any of the excipients of study agent (IP) or standard endocrine therapy drug.
* Each study agent specific exclusion criteria can be found in the agent-specific appendix

Primary outcomes:
measure: Percentage change in Ki67
timeFrame: Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy
Secondary outcomes:
measure: Ki67 <10% on-treatment measurement
timeFrame: 15 or 19 days, based on the duration specified for the assigned therapy
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford Universiy
name: Jennifer Caswell-Jin
role: PRINCIPAL_INVESTIGATOR
References: