An official website of the United States government
Government Funding Lapse Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.
The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov.
Updates regarding government operating status and resumption of normal operations can be found at opm.gov.
Tirzepatide or Semaglutide for the Treatment of Weight Loss in Patients with Endometrial Cancer who are Obese, Overweight, or Diabetic
Trial Status: active
This phase I trial tests how well tirzepatide or semaglutide work for the treatment of patients with endometrial cancer who are obese, overweight, or with or without type 2 diabetes mellitus, and who are undergoing platinum-based chemotherapy. Glucose dependent insulinotropic peptide (GIP) and glucagon like peptide-1 (GLP-1) receptor agonists, such as tirzepatide, and GLP-1 agonists, such as semaglutide, are drugs taken for type 2 diabetes and weight loss, and work by slowing down digestion or causing the stomach to take longer to empty. This increases how full people feel after eating, and reduces overall food intake, appetite, and hunger, which often results in weight loss. Platinum containing compounds, such as carboplatin, paclitaxel, and cisplatin work by killing, stopping or slowing the growth of cancer cells. Giving tirzepatide or semaglutide may work better at treating patients with endometrial cancer who are obese, overweight, or with or without type 2 diabetes mellitus, and who are undergoing platinum-based chemotherapy.
Inclusion Criteria
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of < 2
Obesity (defined as body mass index [BMI] >= 30 kg/m^2) OR overweight (defined as BMI >= 27 kg/m^2) with presence of >= 1 weight related comorbid condition OR a diagnosis of type 2 diabetes mellitus with BMI >= 25 kg/m^2
* If BMI is >= 27 kg/m^2 but < 30 kg/m^2, then at least one weight-related comorbid condition must be present including hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease
* Type 2 diabetes mellitus is defined as known history of type 2 diabetes, HbA1c > 6.5%, fasting blood glucose > 126 mg/dL on 2 occasions, or random blood glucose > 200 mg/dL with signs and symptoms of diabetes mellitus(weight loss, fatigue, polyuria, polydipsia, vision changes)
Patients with new diagnosis of stage I-III endometrial cancer
Completed surgery with total hysterectomy (TH)/bilateral salpingo-oophorectomy (BSO) with no gross residual disease
Recommended to undergo curative intent adjuvant chemotherapy at Memorial Sloan Kettering (MSK) with carboplatin and paclitaxel with or without intravaginal radiation OR cisplatin and concurrent radiation followed by carboplatin and paclitaxel. Patients may consent prior to and up to 3 weeks after the first cycle of chemotherapy
Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, carcinosarcoma, undifferentiated carcinoma/de-differentiated, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), and mucinous adenocarcinoma
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 × upper limit of normal (ULN)
Total serum bilirubin <1.5 × ULN except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is =< 3.0 × ULN or direct bilirubin <= 1.5 × ULN
Insurance approval for tirzepatide or semaglutide (alternative) or willingness to pay out-of-pocket for tirzepatide or semaglutide (alternative) for duration of study period
Patients must be capable and willing to learn how to self-inject study drug, as required for this protocol (visually impaired persons who are not able to perform the injections must have the assistance of a sighted individual trained to inject study drug; persons with physical limitations who are not able to perform the injections must have the assistance of an individual trained to inject study drug) and administer study drug injection (or receive an injection from a trained individual if visually impaired or with physical limitations)
Not pregnant and not nursing
English speaking or a family member or caregiver who speaks English and is able to assist with smart phone or tablet based Keenoa app or paper dietary recall handout (if no access to smart phone or tablet)
Exclusion Criteria
Known type 1 diabetes
Known GAD, Islet Cell, or Zn Transporter 8 antibodies
History of gastroparesis
High risk for aspiration
Active or history of chronic or acute pancreatitis
History of elevated calcitonin
Personal or family history of medullary thyroid carcinoma with multiple endocrine neoplasia-2 syndrome
Patients with a prior surgical, endoscopic, and/or device-based therapy (for example, mucosal ablation, gastric artery embolization, intragastric balloon and duodenal-jejunal bypass sleeve) for obesity within the past two years
Patients with removal of device-based therapy for obesity within the last 6 months
Current GIP/GLP-1 or GLP-1 receptor agonist use or prior intolerance of GIP/GLP-1 or GLP-1 receptor agonist
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Known intolerance to study drug(s) or any of the excipients
Additional locations may be listed on ClinicalTrials.gov for NCT06751589.
I. To determine the feasibility of weekly subcutaneous (SC) tirzepatide treatment during adjuvant chemotherapy with or without radiation among patients with EC as measured by the percentage of patients that complete 70% of more weekly doses.
SECONDARY OBJECTIVES:
I. To determine the patient acceptability of weekly SC tirzepatide treatment during adjuvant chemotherapy with or without radiation among patients with endometrial cancer (EC) as measured by the Acceptability of Intervention Measure.
II. To evaluate the safety of SC tirzepatide during adjuvant chemotherapy with or without radiation among patients with EC by determining gastrointestinal adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
III. To quantify the frequency of chemotherapy delays, missed chemotherapy cycles, or missed radiation doses that are attributed to tirzepatide.
IV. To determine the impact on cardiometabolic outcomes as measured by the change in weight, waist circumference, body fat composition, blood pressure, fasting insulin levels, glycosylated hemoglobin (HbA1c), inflammatory markers, and lipid levels among patients with EC treated with weekly SC tirzepatide.
OUTLINE:
Patients receive tirzepatide or semaglutide SC once a week (QW) concurrently with carboplatin and paclitaxel, with or without intravaginal radiation, or cisplatin concurrently with pelvic radiation for 4 weeks on study. Patients also undergo one nutrition counseling session during this time. Patients then continue to receive tirzepatide or semaglutide SC QW and nutrition counseling once every 4 weeks (Q4W) for up to 24 weeks on study. Additionally, patients undergo computed tomography (CT) scans on study and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
