A Randomized Phase II Evaluation of Continuous Progestin Therapy vs. Sequential Progestin Therapy in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN Patients That Desire Uterine Preservation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 50
- 主要终点
- Number of Patients Who Experience a Response as Determined by a Central Blinded Review of the Three Post Treatment Endometrial
研究概览
简要总结
This randomized phase II trial is studying how well megestrol works in treating patients with endometrial neoplasia or endometrial hyperplasia. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol may fight endometrial cancer by blocking the use of estrogen by the abnormal cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the frequency of complete remission by a central pathology review panel in diagnosed endometrial intraepithelial neoplasia (EIN) patients treated for 24 weeks with oral continuous versus interrupted progestin therapy.
SECONDARY OBJECTIVES:
I. To evaluate whether quality of life is superior in patients who take continuous megestrol versus sequential megestrol by evaluating mood, concerns about weight changes and bleeding.
TERTIARY:
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
- •Patients must have a diagnosis of atypical endometrial hyperplasia (AEH) or endometrial intraepithelial neoplasia (EIN) diagnosed by dilatation and curettage (D&C), Novak curettage, Vabra aspirate, or Pipelle endometrial biopsy at the enrolling institution within 12 weeks of enrollment
- •Patients must desire uterine retention for duration of study (18 months or after 3rd biopsy) if they remain EIN negative (-); patients are allowed to attempt pregnancy after their initial post-treatment biopsy without it being a major protocol violation
- •Patients must have a GOG performance status of 0, 1, or 2
- •White blood cell (WBC) >= 3000
- •Platelets >= 100,000
- •Granulocytes >= 1,500
- •Creatinine =< 2
- •Bilirubin =< 1.5 x institutional upper limit normal
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x institutional upper limit normal
- •Alkaline phosphatase =< 3 x institutional upper limit normal
- •Patients of child-bearing potential must have a negative serum pregnancy test prior to starting study drug and prior to each biopsy if capable of becoming pregnant (and at the discretion of the referring physician)
- •Patients of childbearing potential must use appropriate non-hormonal contraception while on study medication
- •Patients who have met the pre-entry requirements
- •Patients must have signed an approved informed consent and authorization permitting release of personal health information
排除标准
- •Patients with a GOG performance status of 3 or 4
- •Patients with recognized endometrial carcinoma
- •Patients with current or prior history of breast cancer
- •Patients with invasive malignancies, with the exception of nonmelanoma skin cancer who had (or have) any evidence of the other cancer present within the past 5 years or whose previous cancer treatment contraindicates this protocol therapy
- •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded
- •Patients who have received prior chemotherapy for any abdominal or pelvic tumor are excluded
- •Patients who are pregnant or lactating
- •Patients with a history of thrombophlebitis, thromboembolic phenomena, or cerebrovascular disorders within the past 5 years
- •Patients under 18 years of age
研究组 & 干预措施
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Biopsy (Procedure)
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Megestrol Acetate (Drug)
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Pharmacological Study (Other)
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Quality-of-Life Assessment (Other)
Regimen 1 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily every day for 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after completing the megestrol treatment.
干预措施: Therapeutic Conventional Surgery (Procedure)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Biopsy (Procedure)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Megestrol Acetate (Drug)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Pharmacological Study (Other)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Quality-of-Life Assessment (Other)
Regimen 2 (megestrol acetate, surgery)
Patients receive oral megestrol twice daily for two weeks continuously followed by no treatment for two weeks. This course is repeated for a total of 24 weeks. Approximately twelve weeks after treatment starts, clinical blood tests are obtained and research serum and plasma collected. Twenty-four weeks constitutes one course of treatment and a pill count is performed during the 12-week f/u visit and at the completion of the treatment course to determine compliance. After progestin therapy the patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after the megestrol treatment.
干预措施: Therapeutic Conventional Surgery (Procedure)
Regimen 3 (surgery/biopsy)
(Closed as of 6/3/2010) Patients do not receive megestrol. At the discretion of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy anytime between 2-20 weeks after enrollment and randomization.
干预措施: Biopsy (Procedure)
Regimen 3 (surgery/biopsy)
(Closed as of 6/3/2010) Patients do not receive megestrol. At the discretion of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy anytime between 2-20 weeks after enrollment and randomization.
干预措施: Laboratory Biomarker Analysis (Other)
Regimen 3 (surgery/biopsy)
(Closed as of 6/3/2010) Patients do not receive megestrol. At the discretion of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy anytime between 2-20 weeks after enrollment and randomization.
干预措施: Pharmacological Study (Other)
Regimen 3 (surgery/biopsy)
(Closed as of 6/3/2010) Patients do not receive megestrol. At the discretion of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy anytime between 2-20 weeks after enrollment and randomization.
干预措施: Quality-of-Life Assessment (Other)
Regimen 3 (surgery/biopsy)
(Closed as of 6/3/2010) Patients do not receive megestrol. At the discretion of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy anytime between 2-20 weeks after enrollment and randomization.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Number of Patients Who Experience a Response as Determined by a Central Blinded Review of the Three Post Treatment Endometrial
时间窗: Up to 12 months after completion of treatment
Treated and eligible participants. This study had 0 participants that completed treatment, therefore no analysis was done. Study closed prior to completion. Central blinded review was not performed for any participants in the study.
次要结局
- Change in Quality of Life (QOL) Evaluated Using the Hospital Anxiety and Depression Scale (HADS) and the Two Items on Bleeding and Weight Gain(Baseline to up to 12 months)