Combination Tirzepatide and Levonorgestrel Intrauterine Device Therapy for Endometrial Intraepithelial Neoplasia (EIN) and Grade 1 Endometrioid Endometrial Carcinoma: A Pilot Window-of-Opportunity Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Pathologic Response at 6 months from Cycle 1 Day 1
研究概览
简要总结
This single-arm study will evaluate the feasibility, safety, and preliminary efficacy of tirzepatide in combination with standard levonorgestrel intrauterine device (LNG-IUD) therapy in patients with endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid endometrial carcinoma with co-existing obesity and metabolic risk factors. Participants will receive tirzepatide once weekly while continuing standard clinical management with an LNG-IUD. Treatment decisions will remain at the discretion of the treating physician. The primary objective is to evaluate pathologic response at approximately 6 months. Secondary objectives include changes in metabolic parameters, assessing the incidence and severity of adverse events of tirzepatide and LNG-IUD therapy, quality of life assessment, change in weight, and change in BMI.
详细描述
Endometrial cancer is one of the most common gynecologic malignancies in the United States, with an increasing incidence rate. Obesity has been identified as a major risk factor for endometrial carcinogenesis and is prevalent among patients with endometrial intraepithelial neoplasia (EIN) and early-stage endometrial cancer. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA), can cause meaningful weight loss and improvement in metabolic parameters. Levonorgestrel intrauterine device (LNG-IUD) therapy is a standard hormonal treatment for local EIN and grade 1 endometrioid endometrial carcinoma. This single-arm, single-center investigator-initiated study will evaluate the feasibility, safety, and preliminary efficacy of combining tirzepatide with standard LNG-IUD treatment in patients with EIN or grade 1 endometrioid endometrial carcinoma with co-existing obesity and metabolic risk factors. Eligible participants will be enrolled after initial histological confirmation of either EIN or grade 1 endometrioid endometrial carcinoma. Clinical management will remain at the discretion of the treating physician.
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
- •Age ≥ 18 years
- •Histologically confirmed endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid EC
- •BMI ≥ 30 kg/m2
- •Presence of at least one obesity-associated metabolic comorbidity, including:
- •a. Hypertension defined as: i. Documented diagnosis of hypertension, regardless of treatment status, documented in the medical records, or ii. Participants receiving antihypertensive therapy, or iii. BP ≥ 130/80 mmHg over 3 independent measurements, or iv. Single BP ≥ 160/100 mmHg b. Hyperlipidemia defined as: i. Documented diagnosis of hyperlipidemia, regardless of treatment status, documented in the medical record, or ii. Participants receiving lipid-lowering therapy, or iii. Triglycerides > 200 mg/dL, or iv. LDL Cholesterol > 130 mg/dL c. Type 2 Diabetes defined as: i. Documented diagnosis of Type 2 diabetes mellitus, regardless of treatment status, documented in the medical record, or ii. Receiving glucose-lowering therapy, or iii. Impaired glucose tolerance (Hgb A1c > 6.0%) d. Diagnosed with sleep apnea
- •For participants diagnosed with grade 1 endometrioid endometrial carcinoma: clinical stage 1A disease with MRI-confirmed myometrial invasion < 50% and no evidence of metastatic disease
- •For participants with EIN: no evidence of extrauterine disease based on clinically appropriate evaluation
- •Ability to provide informed consent and comply with study procedures and follow-up
- •Mismatch repair-deficient (MMRd) tumors
- •p53-abnormal tumors
- •Known hypersensitivity or contraindication to either:
- •Tirzepatide, or
- •Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis
- •Current systemic progestin therapy
- •Current treatment with tirzepatide or another GLP-1 receptor agonist/GLP-1-GIP receptor agonist, or prior treatment with these agents within 1 month before study enrollment
- •Type 1 diabetes or a history of pancreatitis, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- •Pregnancy, breastfeeding, or intention to become pregnant during the study treatment
- •Concurrent malignancy requiring active treatment (except non-melanoma skin cancer)
- •Any medical, psychiatric, or social condition, that in the opinion of the investigator, would interfere with study participation or safety
- •Participants with diabetic eye disease, including non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema
- •Severe renal impairment, defined as eGFR < 30 mL/min/1.73m2
排除标准
- 未提供
研究组 & 干预措施
LNG-IUD and Tirzepatide Management
Participants will receive tirzepatide in combination with standard clinical management with an LNG-IUD. Tirzepatide will be initiated at 2.5 mg subcutaneously once weekly. Dose escalation will occur according to the study protocol based on participant tolerability and treating physician discretion. Tirzepatide will be administered for approximately 6 months.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Pathologic Response at 6 months from Cycle 1 Day 1
时间窗: At the end Cycle 6 Day 28 (Approximately 6 months from Cycle 1 Day 1with each cycle approximately 28 days)
Pathologic response will be assessed at Cycle 6 Day 28, approximately 6 months after Cycle 1 Day 1, using available clinical pathology specimens, as clinically indicated. For participants undergoing definitive surgical management, pathologic response may be assessed using the hysterectomy specimen. For participants not undergoing hysterectomy, pathologic response may be assessed using an endometrial biopsy or dilation and curettage (D\&C). Pathologic response will be categorized as complete response, partial response, stable disease, or progressive disease.
次要结局
- Change in metabolic parameters(At Baseline, Cycle 4 Day 1, and Cycle 6 Day 28 (each cycle is approximately 28 days))
- Assessing the Incidence and Severity of Adverse Events of Tirzepatide and LNG-IUD therapy(Through study completion, an average of 9 months)
- Quality of Life Assessment Utilizing Study 36-Item Short Form Health Survey (SF-36) Quality of Life Score(Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28)
- Change in Weight(For a total of 6 months from Baseline to Cycle 6 Day 28. Weight will be collected at Baseline, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28 (each cycle is approximately 28 days))
- Change in BMI(For a total of 6 months from Baseline to Cycle 6 Day 28. Weight will be collected at Baseline, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28 (each cycle is approximately 28 days))
研究者
Shaina Bruce
Principal Investigator
Milton S. Hershey Medical Center