Umbrella Trial Testing Integrative Subtype-Targeted Therapeutics in HR+ /HER2-Negative Breast Cancer

Sponsor
Stanford University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05101564
Collaborator
United States Department of Defense (U.S. Fed)
264
1
11
47
5.6

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.

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

Study Type:
Interventional
Anticipated Enrollment :
264 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Umbrella, Randomized, Controlled, Pre-Operative Trial Testing Integrative Subtype-Targeted Therapeutics in Hormone Receptor-Positive, HER2-Negative Breast Cancer
Anticipated Study Start Date :
Jan 1, 2023
Anticipated Primary Completion Date :
Sep 1, 2025
Anticipated Study Completion Date :
Dec 1, 2026

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:
  • Piqray
  • BYL719
  • 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:
  • Soltamox
  • TAM
  • 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:
  • Truseltiq
  • 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:
  • Soltamox
  • TAM
  • 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:
  • Truseltiq
  • 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:
  • Soltamox
  • TAM
  • Experimental: IC9: Amcenestrant

    Integrative subtype 9, Amcenestrant 200 mg

    Drug: Amcenestrant
    Amcenestrant 200 mg
    Other Names:
  • SAR439859
  • 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:
  • SAR439859
  • 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:
  • SAR439859
  • 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

    1. 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

    1. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    • Able to swallow and retain oral medication.

    • 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.

    • 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

    • 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.
    Responsible Party:
    Stanford University
    ClinicalTrials.gov Identifier:
    NCT05101564
    Other Study ID Numbers:
    • IRB-52869
    • BRS0124
    First Posted:
    Nov 1, 2021
    Last Update Posted:
    Jun 14, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 14, 2022