Weight loss treatment for early breast cancer using tirzepatide

Adjuvant Tirzepatide Plus Standard of Care Endocrine Therapy in Patients With Obesity or Overweight Who Have Hormone Receptor-positive, HER2-negative, Node-positive Early Breast Cancer, With Molecular Residual Disease (MRD), as Determined by Circulating Tumor DNA (ctDNA)

This study is testing if the weight loss drug tirzepatide can help overweight or obese women with early breast cancer live longer and healthier by reducing harmful tumor markers in their blood.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Baylor Research Institute (Academic / other)
• Drugs / interventions: denosumab
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT06517212 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates whether weight loss induced by tirzepatide can improve survival outcomes in high-risk early breast cancer patients who are overweight or obese. It focuses on hormone receptor-positive, HER2-negative, node-positive patients and aims to determine if weight loss can lead to the clearance of circulating tumor DNA (ctDNA) and prevent the development of metastatic disease. Participants will be monitored for ctDNA levels and clinical outcomes over a two-year period following treatment. The study will assess the effectiveness of tirzepatide in this specific patient population and its potential impact on disease-free survival.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with node-positive, hormone receptor-positive, and HER2-negative early breast cancer who are overweight or obese.

Not a fit: Patients with early breast cancer who are not overweight or obese, or those with different cancer subtypes may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with early breast cancer who are overweight or obese.

How similar studies have performed: While there is ongoing research into weight loss and cancer treatment, this specific approach using tirzepatide in this patient population is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Female or male patients ≥18 years of age
2. 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

   1. 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
   2. 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%
   3. 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
3. Overweight or obesity defined as body mass index (BMI) \> 27 kg/m2
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5. 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
6. Positive ctDNA blood test as determined by the Haystack Oncology Haystack MRD tumor-informed ctDNA assay
7. 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
8. 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
9. Have adequate hematologic function, defined by:

   1. Absolute neutrophil count (ANC) \>1500/µL
   2. Platelet count ≥100,000/ µL
   3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
10. Have adequate liver function, defined by:

    1. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 x the upper limit of normal (ULN)
    2. Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN
11. Have adequate renal function, defined by:

    a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min
12. Patients must be accessible for treatment and follow-up
13. All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry

Exclusion Criteria:

1. Prior bariatric surgery and/or endoscopic procedures for weight loss (e.g., intragastric balloon, sleeve gastrostomy) following diagnosis of breast cancer
2. 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
3. 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
4. Insulin-dependent diabetes
5. Has clinical evidence of diabetic retinopathy
6. Clinical evidence or suspicion of metastatic breast cancer
7. Current or past invasive cancers, other than breast cancer, are not allowed except for:

   1. Adequately treated basal or squamous cell carcinoma of the skin
   2. 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
8. Patients with a second synchronous primary HER2-positive or triple negative breast cancer
9. Has an active infection requiring systemic therapy
10. Has a known history of human immunodeficiency virus (HIV) or active or persistent hepatitis B or hepatitis C virus
11. Has significant cardiovascular disease, such as:

    1. History of stroke, myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months
    2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV.
12. Has a known history of active tuberculosis
13. Women who are pregnant or lactating. All patients of reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug
14. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as:

    1. severe impaired lung functions as defined as spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
    2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)
    3. history of gastroparesis, impaired gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea vomiting and/or diarrhea, malabsorption syndrome, or small bowel resection)
15. Has a history of pancreatitis or current symptoms of untreated cholelithiasis
16. Has a family history of Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2) or medullary thyroid cancer (MTC)
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's full participation for the full duration of the study, or results in trial participation not being in the patient's best interest, in the opinion of the Treating Physician
18. Has received an investigational agent within 4 weeks prior to study treatment; investigational monoclonal antibodies should have a 4-week (28 day) or 5 half-life washout period
19. Any other investigational or anti-cancer treatments while participating in this study with the exception of standard adjuvant endocrine therapy, zoledronic acid, or denosumab

Where this trial is running

Dallas, Texas

• Baylor University Medical Center, Baylor Charles A Sammons Cancer Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Joyce A O'Shaughnessy, MD — Baylor Scott & White The Heart Hospital
• Study coordinator: CORC Solid Tumor

Conditions Breast Cancer; Breast Neoplasms; Breast Cancers; TRIM; TRIM EBC; TRIM-EBC; tirzepatide; MRD