Prospective, Phase II Study to Evaluate the Efficacy of Addition of Progesterone to Standard Chemotherapy According to Etoposide-Doxorubicin-Cisplatin Scheme Plus Mitotane (EDP-M) in Patients With Advanced Adrenocortical Carcinoma (ACC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Evaluation of the activity of the combination regimen (EDP-M plus progesterone (EDP-MP) versus EDP-M plus placebo) in advanced/ metastatic patients with ACC.
研究概览
简要总结
This is a prospective randomized, double blind, placebo controlled phase II study planned in patients with advanced ACC. The study will be conducted at ASST Spedali Civili Hospital and University of Brescia in Brescia.
详细描述
As no effective second-line therapies are available for patients with disease progression to EDPM, including modern molecular target therapies and immunotherapy, it is reasonable to expect that no newer drugs or combination regimens will be able to replace EDPM in the next 5 years. Since EDP-M is destined to remain the standard first line therapy, research strategies aimed to improve the efficacy of this regimen are of relevance. In this study, investigators will address the hypotheses that progesterone has a synergistic and/or additive effect to EDP-M in inducing cytotoxicity in ACC cells in vitro and the antineoplastic activity of EDP-M in locally advanced/metastatic ACC patients could be improved by the addition of megestrol acetate.
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
- Double (Participant, Investigator)
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
- •Locally advanced or metastatic disease not amenable to radical surgery resection
- •ECOG performance status 0-2
- •Effective contraception
- •Life expectancy > 3 months
- •Age > 18 years
- •Adequate bone marrow reserve (neutrophils >1,000/mm3 and/or platelets >80,000/mm3) and organ function (including renal, liver and cardiac function)
- •Be able to comply with the protocol procedures and provide written informed consent.
排除标准
- •History of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, breast ductal carcinoma in situ, or other treated malignancies where there has been no evidence of disease for at least 2 years
- •Renal insufficiency (estimated glomerular filtration rate [GFR]<50 mL/min/1.73 m2) or significant liver insufficiency (serum bilirubin>2 times the upper normal range and/or serum alanine aminotransferase [ALT] or aspartate aminotransferase [AST]>3 times the upper normal range). GFRs will be calculated according to the validated formula (MDRD)
- •Pregnancy or breast feeding
- •Congestive heart failure (ejection fraction<45%)
- •Preexisting grade 2 peripheral neuropathy
- •Previous or current treatment with mitotane or other antineoplastic drugs for ACC
- •Previous radiotherapy 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 that, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
研究组 & 干预措施
EDP-M plus MEGESTROL ACETATE 160 mg
EDP will be administered at the following doses: doxorubicin 40 mg/m2 on day 1, etoposide 100 mg/m2 days 2-4, cisplatin 40 mg/m2 days 3-4, every 28 days. Concomitant mitotane therapy will be administered continuously. Megestrole 160 mg 2 tablets will be administered once daily (in the morning) and will be stopped 21 days after the last administration of the EDP.
干预措施: Etoposide, doxorubicin, cisplatin and Mitotane plus Megestrol Acetate 160 MG (Drug)
EDP-M plus PLACEBO
EDP will be administered at the following doses: doxorubicin 40 mg/m2 on day 1, etoposide 100 mg/m2 days 2-4, cisplatin 40 mg/m2 days 3-4, every 28 days. Concomitant mitotane therapy will be administered continuously. Placebo 2 tablets will be administered once daily (in the morning) and will be stopped 21 days after the last administration of the EDP.
干预措施: Etoposide, doxorubicin, cisplatin and Mitotane plus Placebo (Drug)
结局指标
主要结局
Evaluation of the activity of the combination regimen (EDP-M plus progesterone (EDP-MP) versus EDP-M plus placebo) in advanced/ metastatic patients with ACC.
时间窗: 18 months
Comparison of proportion of patients attaining an Objective Response (Objective Response Rate, ORR), evaluated by RECIST criteria between the 2 treatment arms.
次要结局
- Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;(18 months)
研究者
Alfredo Berruti
Medical Oncologist
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia