Breast Cancer, HER2-negative Breast Cancer, ER Positive Breast Cancer
Conditions
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)
Interventions
DRUGAlpelisib
Alpelisib 300 mg
DRUGTamoxifen
Tamoxifen 20 mg
DRUGZotatifin
Zotatifin 0.10mg/kg (by weight)
DRUGFulvestrant
Fulvestrant 500 mg
Sponsors
Jennifer Lee Caswell-Jin
United States Department of Defense
Novartis Pharmaceuticals
Effector Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Ki67 | Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy | The primary outcome is the percentage change in Ki67 expression comparing pre-treatment to on-treatment specimens. Ki67 values were log-transformed for analysis, and results are summarized as the mean percentage change with 95% confidence intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ki67 <10% On-treatment Measurement | 15 or 19 days, based on the duration specified for the assigned therapy | The proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJennifer Caswell-Jin
Stanford Universiy
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 7 / 7 | 5 / 8 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 7 | 0 / 8 |
Outcome results
None listed