Umbrella Trial Testing Integrative Subtype Targeted Therapeutics in Estrogen Receptor Positive, HER2-Negative Breast Cancer

Breast Cancer Clinical Trial

Official title:

An Umbrella, Randomized, Controlled, Pre Operative Trial Testing Integrative Subtype Targeted Therapeutics in Estrogen Receptor Positive, HER2-Negative Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05101564
• Other study ID #: IRB-52869
• Secondary ID: BRS0124NCI-2023-
• Status: Recruiting
• Phase: Phase 2
• Start date: March 20, 2023
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: Allison Zhang
• Phone: 650-736-5790
• Email: axkong[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 exclusion criteria can be found in the agent-specific appendix

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• ER Positive Breast Cancer
• HER2-negative Breast Cancer

Intervention

Drug:
• Alpelisib
Alpelisib 300 mg
• Tamoxifen
Tamoxifen 20 mg
• Zotatifin
Zotatifin 0.10mg/kg (by weight)
• Fulvestrant
Fulvestrant 500 mg

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in Ki67	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.	Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy
Secondary	Ki67 <10% on-treatment measurement	The proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion.	15 or 19 days, based on the duration specified for the assigned therapy