Umbrella Trial Testing Integrative Subtype-Targeted Therapeutics in HR+ /HER2-Negative Breast Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
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 or 18 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 or 18 days)
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: IC1:Alpelisib Integrative subtype IC1, Treatment (14 days, - 2 or + 7 days): Take assigned alpelisib pills, 300 mg (two 150 mg tablets) with food, once daily by mouth |
Drug: Alpelisib
Alpelisib 300 mg
Other Names:
|
Active Comparator: IC1:Tamoxifen Integrative subtype 1, Treatment (14 days, -2 to +7 days): Take assigned tamoxifen pills, 20 mg once daily by mouth |
Drug: Tamoxifen
Tamoxifen 20 mg
Other Names:
|
Experimental: IC2:Infigratinib Integrative subtype 2, Treatment (18 days, - 2 to +3 days): Take assigned infigratinib pills, 100 mg once daily by mouth in the morning |
Drug: Infigratinib
Infigratinib 100 mg
Other Names:
|
Active Comparator: IC2:Tamoxifen Integrative subtype 2, Treatment (18 days, - 2 to +3 days): Take assigned tamoxifen pills, 30 mg once daily by mouth |
Drug: Tamoxifen
Tamoxifen 20 mg
Other Names:
|
Active Comparator: IC6:Infigratinib Integrative subtype 2, Treatment (18 days, - 2 to +3 days): Take assigned tamoxifen pills, 30 mg once daily by mouth |
Drug: Infigratinib
Infigratinib 100 mg
Other Names:
|
Active Comparator: IC6:Tamoxifen Integrative subtype 6, Treatment (18 days, - 2 to +3 days): Take assigned tamoxifen pills, 30 mg once daily by mouth |
Drug: Tamoxifen
Tamoxifen 20 mg
Other Names:
|
Experimental: IC9: Amcenestrant Integrative subtype 9, Amcenestrant 200 mg |
Drug: Amcenestrant
Amcenestrant 200 mg
Other Names:
|
Active Comparator: IC9: Letrozole Integrative subtype 9, Letrozole 2.5 mg |
Drug: Letrozole
Letrozole 2.5 mg
|
Experimental: Typical risk: Amcenestrant Integrative subtypes 3, 4, 7, 8, Amcenestrant 200 mg |
Drug: Amcenestrant
Amcenestrant 200 mg
Other Names:
|
Experimental: Typical risk: Amcenestrant + Letrozole Integrative subtypes 3, 4, 7, 8 , Drug: Amcenestrant 200 mg, Drug: Letrozole 2.5 mg |
Drug: Amcenestrant
Amcenestrant 200 mg
Other Names:
Drug: Letrozole
Letrozole 2.5 mg
|
Active Comparator: Typical risk: Letrozole Integrative subtypes 3, 4, 7, 8, Drug: Letrozole 2.5 mg |
Drug: Letrozole
Letrozole 2.5 mg
|
Outcome Measures
Primary Outcome Measures
- 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 for this study is the change in digital pathology software-assessed quantitative Ki67 IHC from pre-treatment specimen to the on-treatment specimen. For analysis purposes, the change in Ki67 will be assessed on log-transformed values. The outcome will be expressed as mean and standard deviation.
Secondary Outcome Measures
- 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.
Eligibility Criteria
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.
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Women or men, age ≥ 18 years old.
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Able to swallow and retain oral medication.
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Performance status 0 to 1 (by Eastern Cooperative Oncology Group [ECOG] scale).
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Ability to understand and the willingness to sign a written informed consent document.
Treatment Phase
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Breast tumor classifies as relevant integrative subtype per tumor sequencing performed and analyzed by central laboratory.
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Breast tumor Ki67 score ≥ 10% as assessed by central laboratory.
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Each investigational agent specific inclusion criteria can be found in the agent-specific appendix
Exclusion Criteria:
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Pregnant woman, as confirmed by positive serum hCG test prior to initiating study treatment. Nursing (lactating) woman also not allowed.
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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.
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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.
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Impairment of gastrointestinal function or gastrointestinal disease that may significant alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion
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Each study agent specific exclusion criteria can be found in the agent-specific appendix
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford University | Stanford | California | United States | 94304 |
Sponsors and Collaborators
- Stanford University
- United States Department of Defense
Investigators
- Principal Investigator: George Sledge, Stanford Universiy
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-52869
- BRS0124