Tirzepatide for Breast Cancer and Obesity

(TRIM-EBC Trial)

Overseen by Joyce A O'Shaughnessy, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Baylor Research Institute

Must be taking: Endocrine therapy

Must not be taking: GLP-1 agonists

Disqualifiers: Bariatric surgery, Insulin-dependent diabetes, Metastatic cancer, Cardiovascular disease, others

No Placebo Group

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken certain weight loss medications or treatments like GLP-1 receptor agonists in the last 3 months, and you cannot be on investigational or anti-cancer treatments other than standard adjuvant endocrine therapy, zoledronic acid, or denosumab.

What data supports the effectiveness of the drug Tirzepatide for breast cancer and obesity?

Research shows that Tirzepatide, a drug that targets specific hormones, helps control blood sugar and leads to significant weight loss in people with type 2 diabetes and obesity. While this data is not directly about breast cancer, the weight loss effects could be beneficial for patients with obesity. ^{1 2 3 4 5}

What makes the drug tirzepatide unique for breast cancer and obesity?

Tirzepatide is unique because it is a dual-action drug that targets both the GIP and GLP-1 receptors, which are involved in regulating insulin and appetite. This dual mechanism is novel compared to other treatments, especially since it is primarily used for type 2 diabetes and weight loss, and its application for breast cancer and obesity is still being explored. ^{2 5 6 7 8}

Research Team

Joyce A O'Shaughnessy, MD

Principal Investigator

Baylor Scott and White Research Institute

Eligibility Criteria

This trial is for individuals with obesity or overweight who have high-risk early breast cancer that's hormone receptor-positive, HER2-negative, and node-positive. They must also have detectable circulating tumor DNA (ctDNA) indicating the presence of micrometastatic disease.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

Accessible for treatment and follow-up

I am 18 years old or older.

Exclusion Criteria

Use of other investigational or anti-cancer treatments during the study

I have been diagnosed with diabetic retinopathy.

My family has a history of MEN 2 or medullary thyroid cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 years

Every 3 months

Treatment

Participants receive tirzepatide once weekly, starting with 2.5mg and increasing by 2.5mg monthly over 6 months, for up to 2 years

Up to 2 years

Monthly for the first 6 months, then every other month

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for distant disease-free survival and exploratory molecular changes

5 years

Treatment Details

Interventions

• Tirzepatide (Other)

Trial Overview The trial is testing whether Tirzepatide can help patients lose at least 10% body weight and if this weight loss leads to metabolic and hormonal changes that may stop the growth of tiny cancer spreadings and clear ctDNA, potentially preventing metastatic disease.

Participant Groups

Group I: tirzepatide Experimental Treatment 1 Intervention

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.

Tirzepatide is already approved in Canada for the following indications:

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Baylor Research Institute

Lead Sponsor

Trials

210

Recruited

205,000+

Findings from Research

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed greater improvements in glucose control and weight loss compared to the GLP-1 receptor agonist dulaglutide in a study involving 316 participants with type 2 diabetes.

The improvements in insulin sensitivity and beta-cell function with tirzepatide were only partially linked to weight loss, indicating that its dual receptor action provides unique mechanisms for better glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. Thomas, MK., Nikooienejad, A., Bray, R., et al.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

Tirzepatide, a medication for type 2 diabetes, shows a dose-dependent increase in gastrointestinal adverse events (AEs), with nausea and diarrhea being the most common, affecting up to 49% of participants at the highest dose (15 mg).

Despite the gastrointestinal side effects, serious adverse events like severe hypoglycemia and acute pancreatitis are rare (≤ 1%), indicating that tirzepatide is generally safe for use in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. Mishra, R., Raj, R., Elshimy, G., et al.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, has a safety profile similar to other GLP-1 receptor agonists, but higher doses (10mg and above) are associated with increased risks of hypoglycemia and treatment discontinuation.

In clinical trials involving 9818 patients, higher doses of tirzepatide led to more frequent gastrointestinal side effects like nausea, vomiting, and diarrhea, indicating that these adverse events are dose-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable? Meng, Z., Yang, M., Wen, H., et al.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable? [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023]