Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 200
- 试验地点
- 28
- 主要终点
- Disease Free survival
研究概览
简要总结
Study Rationale Adrenocortical carcinoma (ACC) is a very rare disease with a high risk of relapse after radical surgery. The efficacy of adjuvant mitotane treatment is suggested by a retrospective multicenter international study showing that postoperative mitotane treatment was associated with a significant reduction of the risk of relapse and death. However, these promising results need confirmation in a randomized prospective study. Caution should be adopted particularly in patients with low risk of disease relapse, in whom the benefit of therapy should be weighted against the side effects. Even if an adjuvant treatment seems justified in patients at high risk of relapse, a randomised prospective study is needed to assess whether such a treatment is efficacious in patients at low-intermediate risk.
The purpose of the present study is to determine whether adjuvant mitotane treatment is effective in prolonging the disease free survival in patients with adrenocortical carcinoma at low-intermediate risk of progression who underwent radical resection
详细描述
Endpoints Primary : To compare DFS (Disease Free Survival), defined as the time between the date of randomization until documentation of any of the following failures (whichever occurs first): -local or distant recurrence of disease;-death from any cause or completion of follow-up.
Secondary:
To compare OS (Overall Survival), defined as the time interval between the date of randomization and the date of death from any cause or the last known alive date;· To compare quality of life measured by EORTC-QLQ-C30· To compare toxicity, graded according to the NCI-CTG criteria;· To compare DFS and OS in patients who achieve or not serum mitotane concentrations > 14 mg/L;· To compare DFS and OS between the 2 arms in patients subgroups stratified according to: type of hormone secretion, stage of disease, histopathologic characteristics.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of ACC according to Weiss system by a national reference pathologist who has to be nominated before study initiation.
- •Low-intermediate risk of relapse defined as:
- •Stage I-III (according to ENSAT classification 2008; see Appendix 2)
- •Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging. Detailed pathological and surgical reports prepared according to guidelines detailed in appendix x and y should be available for assessment.
- •Ki 67 < 10%
- •Post-operative imaging (thoracic and whole abdominal CT with contrast medium or MRI) demonstrating no evidence of disease within 4 weeks from randomization
- •Age > 18 years
- •ECOG performance status 0-2 (Appendix 3)
- •Adequate bone marrow reserve (neutrophils > 1000/mm3 and platelets > 80000/ mm3)
- •Ability to comply with the protocol procedures (including geographic accessibility)
- •Written informed consent
排除标准
- •Time between primary surgery and randomization > 3 months.
- •Repeat surgery for recurrence of disease
- •Presence of autonomous adrenocortical hormone secretion despite the absence of disease detectable with imaging techniques
- •History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years
- •Renal insufficiency (creatinine clearance < 40 ml/min) or liver insufficiency (serum bilirubin > 2 times the upper normal range and/or serum transaminases (AST/SGOT, ALT/SGPT, but not gamma Glutamyl Transpeptidase) >3 times the upper normal range). Creatinine clearance may be calculated according to validated formulas (Crockoft's or MDRD)
- •Pregnancy or breast feeding
- •Previous or current treatment with mitotane or other antineoplastic drugs for ACC
- •Previous radiotherapy of the tumor bed (for ACC).
- •Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
研究组 & 干预措施
Mitotane
Arm A
干预措施: MITOTANE (Drug)
结局指标
主要结局
Disease Free survival
时间窗: Till the last follow up
Survival in years
次要结局
未报告次要终点
研究者
Alfredo Berruti
Prof.
University of Turin, Italy