Tirzepatide Weight Loss for MRD+ Early Breast Cancer

NCT06517212 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 024-273
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This trial aims to asses if tirzepatide-induced weight loss will lead to metabolic and hormonal changes in hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-), node-positive (N+) high risk early breast cancer patients with obesity or overweight, inhibiting the growth and survival of micrometastatic disease and leading to clearance of tumor-informed circulating tumor DNA (ctDNA) and freedom from the development of metastatic disease.

Conditions

Breast Cancer; Breast Neoplasms; Breast Cancers

Keywords

TRIM; TRIM EBC; TRIM-EBC; tirzepatide; MRD; ctDNA

Outcome Measures

Primary Outcomes (2)

• ctDNA efficacy

  Clearance of the presence of plasma ctDNA within two years of documented ctDNA positivity at time of study entry.

  2 years

• distant disease-free survival efficacy

  Percentage of patients alive and free of distant metastatic disease at 2 years following detection of ctDNA at the time of study entry.

  2 years

Secondary Outcomes (3)

• ctDNA kinetic changes using Haystack MRD

  2 years

• Number of patients with Treatment-Related Adverse Events (Safety and Tolerability)

  2 years

• weight loss

  2 years

Other Outcomes (2)

• time to recurrence

  5 years

• exploratory molecular changes via Next Generation Sequencing (NGS), Flow Cytometry, and Reverse Phase Protein Array (RPPA)

  5 years

Study Arms (1)

tirzepatide

EXPERIMENTAL

Patients will be treated with tirzepatide 15mg subcutaneously (SC) weekly (starting with 2.5mg SC weekly and increasing by 2.5mg monthly over 6 months) and will be monitored closely for tolerability, safety, and weight loss. Patients may be treated with tirzepatide for up to 2 years on trial if they remain without evidence of metastatic disease recurrence and provided there's demonstrated safety of tirzepatide with associated weight loss.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Patients will receive tirzepatide once weekly for up to 2 years.

Also known as: ZepBound

tirzepatide

Eligibility Criteria

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

You may qualify if:

• Female or male patients ≥18 years of age
• Have a diagnosis of node-positive, hormone receptor-positive (ER+ \> 10%), and HER2-negative breast cancer within the past 15 years per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• If patients have synchronous bilateral ER+ breast cancers, tissue from both primary cancers should be submitted for next-generation sequencing (NGS) to inform ctDNA testing
• Patients with multifocal/multicentric cancers are eligible and the largest focus of cancer should be submitted for NGS evaluation. If tested, all tumor foci must meet have ER \> 10%
• For patients who received neoadjuvant therapy and have discordant hormone receptor and/or HER2 results between the diagnostic biopsy (pre-treatment) and the surgical pathology (post-neoadjuvant treatment), the hormone receptor status and HER2 status of the post-treatment specimen will determine eligibility
• Overweight or obesity defined as body mass index (BMI) \> 27 kg/m2
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Have received at least 1 year of or having completed standard neo/adjuvant endocrine therapy. If adjuvant cyclin dependent kinase (CDK) 4/6 inhibitor therapy was prescribed, patients must have completed this therapy
• Positive ctDNA blood test as determined by the Haystack Oncology Haystack MRD tumor-informed ctDNA assay
• Patients must have formalin-fixed paraffin-embedded (FFPE) tissue from the primary tumor available for submission to Haystack Oncology to perform whole genome sequencing (WGS) to build customized mutation panel to monitor for plasma ctDNA
• No clinical evidence of metastatic breast cancer found on history, physical examination, complete blood count (CBC), comprehensive metabolic panel (CMP), and radiologic imaging following a finding of positive ctDNA
• Have adequate hematologic function, defined by:
• Absolute neutrophil count (ANC) \>1500/µL
• Platelet count ≥100,000/ µL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

You may not qualify if:

• Prior bariatric surgery and/or endoscopic procedures for weight loss (e.g., intragastric balloon, sleeve gastrostomy) following diagnosis of breast cancer
• Treatment with a GLP-1/Glucagon receptor agonist, GIP/GLP-1/Glucagon receptor agonist, GIP/GLP receptor agonist, or any combinations with GLP-1 receptor agonist therapies within the last 3 months
• History of severe hypersensitivity reaction to GLP-1/Glucagon receptor agonist, GIP/GLP-1/Glucagon receptor agonist, or any combinations with GLP-1 receptor agonist therapies
• Insulin-dependent diabetes
• Has clinical evidence of diabetic retinopathy
• Clinical evidence or suspicion of metastatic breast cancer
• Current or past invasive cancers, other than breast cancer, are not allowed except for:
• Adequately treated basal or squamous cell carcinoma of the skin
• Previously diagnosed invasive cancer treated with curative intent, with no evidence of disease recurrence for at least 5 years, and are considered low risk for future recurrence by the treating physician
• Patients with a second synchronous primary HER2-positive or triple negative breast cancer
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) or active or persistent hepatitis B or hepatitis C virus
• Has significant cardiovascular disease, such as:
• History of stroke, myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months
• Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV.

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (1)

Baylor University Medical Center, Baylor Charles A Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Joyce A O'Shaughnessy, MD

  Baylor Scott and White Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CORC Solid Tumor

CONTACT

214-818-8472; corcsolidtumor@bswhealth.org

Page E Blas, MA

CONTACT

214-820-5424; page.blas@bswhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: July 24, 2024
• Study Start: November 26, 2024
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (1)