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

NCT05101564 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-52869NCI-2023-02578
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Ki67

  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.

  Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy

Secondary Outcomes (1)

• Ki67 <10% On-treatment Measurement

  15 or 19 days, based on the duration specified for the assigned therapy

Study Arms (14)

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

EXPERIMENTAL

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

Drug: Alpelisib; Drug: Tamoxifen

IC1:Tamoxifen (closed to enrollment)

ACTIVE COMPARATOR

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

Drug: Tamoxifen

IC2:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC2:Fulvestrant

ACTIVE COMPARATOR

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.

Drug: Fulvestrant

IC3:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC3:Fulvestrant

ACTIVE COMPARATOR

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.

Drug: Fulvestrant

IC4:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC4:Fulvestrant

ACTIVE COMPARATOR

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..

Drug: Fulvestrant

IC6:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC6:Fulvestrant

ACTIVE COMPARATOR

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.

Drug: Fulvestrant

IC7:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC7:Fulvestrant

ACTIVE COMPARATOR

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.

Drug: Fulvestrant

IC8:Zotatifin in combination with Fulvestrant

EXPERIMENTAL

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.

Drug: Zotatifin; Drug: Fulvestrant

IC8:Fulvestrant

ACTIVE COMPARATOR

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.

Drug: Fulvestrant

Interventions

Alpelisib DRUG

Alpelisib 300 mg

Also known as: Piqray, BYL719

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

Tamoxifen DRUG

Tamoxifen 20 mg

Also known as: Soltamox, TAM

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

Zotatifin DRUG

Zotatifin 0.10mg/kg (by weight)

Also known as: eFT226

IC2:Zotatifin in combination with Fulvestrant; IC3:Zotatifin in combination with Fulvestrant; IC4:Zotatifin in combination with Fulvestrant; IC6:Zotatifin in combination with Fulvestrant; IC7:Zotatifin in combination with Fulvestrant; IC8:Zotatifin in combination with Fulvestrant

Fulvestrant DRUG

Fulvestrant 500 mg

Also known as: Faslodex

IC2:Fulvestrant; IC2:Zotatifin in combination with Fulvestrant; IC3:Fulvestrant; IC3:Zotatifin in combination with Fulvestrant; IC4:Fulvestrant; IC4:Zotatifin in combination with Fulvestrant; IC6:Fulvestrant; IC6:Zotatifin in combination with Fulvestrant; IC7:Fulvestrant; IC7:Zotatifin in combination with Fulvestrant; IC8:Fulvestrant; IC8:Zotatifin in combination with Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jennifer Lee Caswell-Jin: lead
• Novartis Pharmaceuticals: collaborator
• Effector Therapeutics: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib; Tamoxifen; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Jennifer Lee Caswell-Jin
• Organization: Stanford University

caswell@stanford.edu

(650) 498-6000

Study Officials

• Jennifer Caswell-Jin

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Oncology)

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 1, 2021
• Study Start: March 20, 2023
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: February 12, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)