A Pre-Operative Window Study of Tirzepatide in Obesity-Driven Endometrial Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Proliferation
研究概览
简要总结
LCCC2415 examines the antiproliferative effect of tirzepatide on the endometrium of endometrial cancer (EC). This is a pre-operative window clinical study. Endometrial biopsy samples from patients before tirzepatide treatment will be compared to their post-intervention hysterectomy specimens. If archival tissue is unavailable, a fresh biopsy will be taken before tirzepatide treatment. Post-intervention tissue will be collected from the hysterectomy specimen.
The hypothesis is that tirzepatide's anti-tumorigenic effects are due to both an improvement in the host's metabolic milieu (indirect effect) and a direct effect on the EC tumor microenvironment via the inter-related pathways of insulin, lipid, and mTOR signaling. Therefore, tirzepatide may be an innovative approach to effectively induce weight loss and inhibit tumor growth in EC, the most obesity-driven of all cancers.
详细描述
The primary objective is to determine if tirzepatide decreases proliferation in the tumors of EC patients. The effect of tirzepatide on the endometrium of 20 obese women with EC will be evaluated by comparing each patient's endometrial biopsy before tirzepatide treatment to their post-treatment hysterectomy specimen, through a pre- operative window study. These women will begin tirzepatide treatment for 4 weeks prior to standard-of-care (SOC) surgery. Subjects will have a single end-of-treatment visit 4 weeks after completing therapy and will be followed for 24 months via medical record abstraction to monitor weight loss maintenance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Current diagnosis of endometrioid histology cancer and scheduled to undergo hysterectomy and staging.
- •Agree to comply with all required study assessments and visits including internet capabilities.
- •Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- •Age ≥ 18 at the time of consent.
- •Body mass index of ≥30 kg/m
- •Presumed clinically early-stage disease (disease confined to uterus only).
- •ECOG ≤ 2 or Karnofsky Performance Status of > 50
排除标准
- •Active infection requiring systemic therapy.
- •Subject is pregnant or breast feeding.
- •Taking any prescription medications or other drugs that may influence metabolism per discretion of investigator.
- •Taking a central nervous system stimulant.
- •Current psychological conditions that would be incompatible with participation in this study, as determined by investigator.
- •Known sensitivities (i.e., urticaria and eczema) to GIP and GLP-1 receptor agonists.
- •Have type 1 diabetes mellitus or latent autoimmune diabetes in adults or receiving treatment with insulin.
- •Have a history of severe hypoglycemia or not be able to communicate an understanding of hypoglycemic symptoms.
研究组 & 干预措施
endometrial carcinoma
Obese women with endometrial carcinoma are included.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Change in Proliferation
时间窗: Baseline - Up to 6 weeks
Change in Proliferation will be determined by immunohistochemical ( Ki-67 staining) analysis pre- (baseline) and post-tirzepatide treatment hysterectomy samples (at the time of surgery and end of treatment). The percentage of tumor cells that are positive for Ki-67, indicating they are in the active phases of the cell cycle (not resting). Low Ki-67 (\<10-15%): Slower-growing tumor. Intermediate (15-30%): Moderately proliferative. High (\>30%): Fast-growing, potentially more aggressive.
次要结局
- Improvement in Diabetes(Baseline - Up to 6 weeks)
- Improvement in HgbA1C level(Baseline - Up to 6 weeks)
- Improvement in waist-to-hip ratio(Baseline - Up to 6 weeks)
- Improvement in Body Mass Index(Baseline - Up to 6 weeks)
- Change in circulating levels of inflammatory cytokines(Baseline - Up to 6 weeks)
- Change in sex hormones(Baseline - Up to 6 weeks)
- Change in Lipids(Baseline - Up to 6 weeks)
- Change in insulin(Baseline - Up to 6 weeks)
- Change in Insulin-like Growth Factor 1(Baseline - Up to 6 weeks)
- Change in glucose(Baseline - Up to 6 weeks)
- Change in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Gamma-Glutamyl Transferase (GGT) levels(Baseline - Up to 6 weeks)
- Change in Apoptosis(Baseline - Up to 6 weeks)
- Change in Ribonucleic Acid (RNA) sequence(Baseline - Up to 6 weeks)