Tirzepatide for Breast Cancer and Obesity

(TRIM-EBC Trial)

Overseen By Page E Blas, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: Up to 2 years

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called tirzepatide (also known as Mounjaro, Zepbound, or LY3298176) to determine its effectiveness for individuals with certain types of breast cancer who are also overweight or obese. The goal is to assess whether weight loss with tirzepatide can alter metabolism and hormones to help prevent cancer from spreading. The trial seeks participants with breast cancer that tests positive for certain hormone receptors but negative for the HER2 protein, has spread to nearby lymph nodes, and have a body mass index above 27. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that tirzepatide is likely to be safe for humans?

Research has shown that tirzepatide is generally safe for people. One study found that it helped adults with obesity lose weight, even without diabetes. This study also found no increased cancer risk from using tirzepatide.

Some people experienced mild side effects like nausea and diarrhea, but overall, the treatment was well-tolerated. Tirzepatide is already approved for treating diabetes under the name Mounjaro, supporting its safety. So far, studies suggest it is a safe option for weight loss in people with obesity. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer and obesity?

Tirzepatide is unique because it combines two hormones, GLP-1 and GIP, to regulate blood sugar and appetite, which could be especially beneficial for breast cancer patients struggling with obesity. Unlike traditional treatments like chemotherapy, which directly target cancer cells, tirzepatide focuses on weight loss and metabolic health, potentially improving overall outcomes and quality of life. Researchers are excited about this treatment because it not only aims to manage weight but also holds potential in reducing cancer recurrence, offering a dual benefit that's different from existing therapies.

What evidence suggests that tirzepatide might be an effective treatment for breast cancer and obesity?

Research shows that tirzepatide, the treatment under study in this trial, aids in weight loss and obesity management. Studies have found it can reduce body weight and fat by about 20% in mice. In humans, clinical trials demonstrated that tirzepatide increases insulin production and outperforms similar treatments. Although limited evidence exists regarding breast cancer, the drug's weight loss benefits might influence survival rates in early breast cancer patients. Overall, tirzepatide has shown promising effects for weight loss, potentially benefiting those with obesity-related health issues. ^{3 4 6 7 8}

Who Is on the Research Team?

Joyce A O'Shaughnessy, MD

Principal Investigator

Baylor Scott and White Research Institute

Are You a Good Fit for This Trial?

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

My blood test for cancer DNA, using the Haystack method, is positive.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tirzepatide

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.

How Is the Trial Designed?

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 United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

Who Is Running the Clinical Trial?

Baylor Research Institute

Lead Sponsor

Trials

210

Recruited

205,000+

Published Research Related to This Trial

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, 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, 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 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, 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40869064/

GLP-1 Receptor Agonists in Breast Cancer: A New Frontier ... Preliminary data suggest that GLP-1 RA use does not increase the risk of cancer recurrence and may reduce cardiovascular morbidity. However, ...

2. endocrine.org endocrine.org/news-and-advocacy/news-room/endo-annual-meeting/endo-2025-press-releases/kucinskas-press-release

Mouse study finds tirzepatide slowed obesity-associated ... The researchers found that the anti-obesity drug reduced body weight and body fat by approximately 20% in mice, similar to the amount of weight ...

3. sciencedaily.com sciencedaily.com/releases/2025/07/250715043353.htm

Weight-loss wonder drug Mounjaro/Zepbound shrinks ... The researchers found that the anti-obesity drug reduced body weight and body fat by approximately 20% in mice, similar to the amount of weight ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822209

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... Subsequent clinical trials confirmed that tirzepatide was more effective than selective GLP-1 agonists in increasing insulin secretion and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06517212

Tirzepatide Weight Loss for MRD+ Early Breast Cancer ... The goal of this clinical trial is to learn if tirzepatide induced weight loss effects survival outcomes in high risk early breast cancer patients. The main ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12186097/

The Impact and Safety of GLP‐1 Agents and Breast Cancer Another study analyzed the effect of semaglutide, liraglutide, dulaglutide and tirzepatide on weight loss outcomes in breast cancer patients who ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206038

Tirzepatide Once Weekly for the Treatment of Obesity The present trial, SURMOUNT-1, evaluated the efficacy and safety of tirzepatide in adults with obesity or overweight who did not have diabetes.

8. e-enm.org e-enm.org/journal/view.php?number=2572

Tirzepatide and Cancer Risk in Individuals with and without ... Tirzepatide use was associated with a similar risk of any cancer to the pooled control (RR, 0.78; 95% CI, 0.53 to 1.16; I 2 =0%; P=0.22, high certainty of ...