Open-Label Randomized Phase II Trial of Megestrol Acetate With or Without Pterostilbene in Patients With Endometrial Cancer Scheduled for Hysterectomy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Tumor Ki-67 Proliferation Index
研究概览
简要总结
This phase II trial studies how well megestrol acetate with or without pterostilbene works in treating patients with endometrial cancer undergoing hysterectomy. Drugs used in chemotherapy, such as megestrol acetate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pterostilbene is an antioxidant found in blueberries or grapes, and it has been shown to be effective in killing tumor cells and reducing cancer burden. It is not yet known whether giving megestrol acetate with or without pterostilbene may work better in treating patients with endometrial cancer.
详细描述
PRIMARY OBJECTIVE:
I. Determine the effect of megestrol acetate (MA) plus pterostilbene (PTE) versus MA alone on tumor proliferation (Ki-67) during the preoperative window in patients with endometrial cancer (EC) who are scheduled for hysterectomy.
EXPLORATORY OBJECTIVES:
I. Determine the effect of MA plus PTE versus MA alone on histologic response during the preoperative window in patients with EC or endometrial complex atypical hyperplasia who are scheduled for hysterectomy.
II. Explore biological characteristics of tumors to determine potential biomarkers which could select for treatment eligibility in future studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Documented informed consent of the participant and/or legally authorized representative
- •Willing to undergo an intraoperative biopsy/or standard of care tissue collection during surgery, following completion of treatment with MA +/- PTE
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Histologically confirmed EC or complex atypical hyperplasia of the endometrium
- •Candidate for a total hysterectomy with or without bilateral salpingo-oophorectomy
- •About to initiate preoperative window period, with planned hysterectomy scheduled
- •Platelets >= 100,000/mm^3
- •NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
- •Total bilirubin =< 1.5 X upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) =< 1.5 x ULN
- •Alanine aminotransferase (ALT) =< 1.5 x ULN
- •Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
- •Women of childbearing potential: negative urine or serum pregnancy test in premenopausal women. Postmenopausal women do not need to undergo a pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
排除标准
- •Pterostilbene supplements within 30 days prior to day 1 of protocol therapy
- •Any of the following phytochemical-based supplements within 30 days prior to day 1 of protocol therapy: resveratrol, genistein, and quercetin
- •Chemotherapy for EC
- •Allergic reaction/hypersensitivity to similar agents, excipients
- •Unstable cardiac disease as defined by one of the following:
- •Cardiac events such as myocardial infarction (MI) within the past 6 months
- •NYHA (New York Heart Association) heart failure class III-IV
- •Uncontrolled atrial fibrillation or hypertensive emergency/urgency (defined as systolic blood pressure >= 180 mmHg and/or diastolic blood pressure >= 120 mmHg)
- •Active or history of recent thromboembolism or stroke, within the past 6 months
- •Cushing's syndrome
- •Acute infection requiring systemic (intravenous) treatment
- •Known history of human immunodeficiency virus (HIV) infection
- •Known active hepatitis B or C infection
- •Inability to swallow tablets/capsules
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Arm II (megestrol acetate)
Patients receive megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.
干预措施: Megestrol Acetate (Drug)
Arm I (pterostilbene, megestrol acetate)
Patients receive 100mg pterostilbene BID and 80mg megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.
干预措施: Megestrol Acetate (Drug)
Arm I (pterostilbene, megestrol acetate)
Patients receive 100mg pterostilbene BID and 80mg megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.
干预措施: Pterostilbene (Biological)
结局指标
主要结局
Tumor Ki-67 Proliferation Index
时间窗: Pre- and post-treatment up to 6 weeks
Ki-67 represents a specific nuclear marker for cell proliferation that is measured by staining with specific antibodies by immunohistochemical (IHC) staining. The Ki-67 proliferation index is defined as percent tumor cells staining positive, and measured on a continuous scale of 0-100%, with higher values indicating higher proliferation. Ki-67 hotspot values were assessed at two time-points during this study, prior to treatment with megace +/- pterostilbene (pre-treatment), and following completion of treatment (post-treatment). Descriptive statistics were used to compare treatment-associated percent change in Ki-67 proliferation index between the 2 study arms, using a 1-sided test with significance at p \< 0.05.
次要结局
- Histologic Response of Gland Cellularity(Up to 6 weeks)
- Histologic Response of Eosinophilic Metaplasia(Up to 6 weeks)
- Histologic Response of Mitotic Index(Up to 6 weeks)
- Histologic Response of Metaplasia(Up to 6 weeks)
- Immunohistochemical Expression of Bcl-2 to Assess Tumor Growth and Apoptosis(Pre- and post-treatment up to 6 weeks)
- Immunohistochemical Expression of Casp3 to Assess Tumor Growth and Apoptosis(Pre- and post-treatment up to 6 weeks)