Umbrella Trial of Subtype-Targeted Therapies in ER+/HER2- Breast Cancer

NCT ID: NCT05101564

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-20
• Study Completion Date: 2026-12-31

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)

Conditions

Breast Cancer; HER2-negative Breast Cancer; ER Positive Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IC1:Alpelisib in combination with Tamoxifen (closed to enrollment)

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. Tamoxifen pills, 20 mg once daily by mouth

Group Type: EXPERIMENTAL

Alpelisib

Intervention Type: DRUG

Alpelisib 300 mg

Tamoxifen

Intervention Type: DRUG

Tamoxifen 20 mg

IC1:Tamoxifen (closed to enrollment)

Integrative subtype 1, Treatment (14 days, -2 to +7 days): Take assigned tamoxifen pills, 20 mg once daily by mouth

Group Type: ACTIVE_COMPARATOR

Tamoxifen

Intervention Type: DRUG

Tamoxifen 20 mg

IC2:Zotatifin in combination with Fulvestrant

Integrative subtype 2, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC2:Fulvestrant

Integrative subtype 2, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC3:Zotatifin in combination with Fulvestrant

Integrative subtype 3, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC3:Fulvestrant

Integrative subtype 3, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. on Day 1.

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC4:Zotatifin in combination with Fulvestrant

Integrative subtype 4, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC4:Fulvestrant

Integrative subtype 4, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1..

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC6:Zotatifin in combination with Fulvestrant

Integrative subtype 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC6:Fulvestrant

Integrative subtype 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC7:Zotatifin in combination with Fulvestrant

Integrative subtype 7, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC7:Fulvestrant

Integrative subtype 7, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC8:Zotatifin in combination with Fulvestrant

Integrative subtype 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: EXPERIMENTAL

Zotatifin

Intervention Type: DRUG

Zotatifin 0.10mg/kg (by weight)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

IC8:Fulvestrant

Integrative subtype 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg

Interventions

Alpelisib

Alpelisib 300 mg

Intervention Type: DRUG

Tamoxifen

Tamoxifen 20 mg

Intervention Type: DRUG

Zotatifin

Zotatifin 0.10mg/kg (by weight)

Intervention Type: DRUG

Fulvestrant

Fulvestrant 500 mg

Intervention Type: DRUG

Other Intervention Names

Piqray; BYL719; Soltamox; TAM; eFT226; Faslodex

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Effector Therapeutics

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Caswell-Jin

Role: PRINCIPAL_INVESTIGATOR

Stanford Universiy

Locations

Stanford University

Stanford, California, United States

Countries

United States

Other Identifiers

NCI-2023-02578

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-52869

Identifier Type: -

Identifier Source: org_study_id