Treatment of Adrenocortical Tumors With Surgery Plus Lymph Node Dissection and Multiagent Chemotherapy: A Groupwide Phase III Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 91
- 主要终点
- Five Year Event-free Survival (EFS)
研究概览
简要总结
This phase III clinical trial is studying how well cisplatin-based chemotherapy and/or surgery works in treating young patients with stage I, stage II, stage III or stage IV adrenocortical cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.
详细描述
PRIMARY OBJECTIVES:
I. Describe the outcome of patients with stage I adrenocortical tumor (ACT) treated with surgery alone.
II. Describe the outcome of patients with stage II ACT treated with radical adrenalectomy plus regional retroperitoneal lymph node dissection.
III. Describe the outcome of patients with unresectable or metastatic ACT treated with mitotane and a cisplatin-based chemotherapy regimen.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adrenocortical carcinoma
- •Newly diagnosed disease within the past 3 weeks
- •Any disease stage allowed
- •Lansky performance status 60-100% (for patients ≤ 16 years old)
- •Karnofsky performance status 60-100% (for patients > 16 years old)
- •Absolute neutrophil count ≥ 750/mm^3
- •Platelet count ≥ 75,000/mm^3
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age as follows:
- •0.4 mg/dL (1 month to < 6 months)
- •0.5 mg/dL (6 months to < 1 year of age)
- •0.6 mg/dL (1 to < 2 years of age
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST or ALT < 2.5 times ULN
- •Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No previous chemotherapy for adrenocortical carcinoma
排除标准
- 未提供
研究组 & 干预措施
Stratum I (surgery, observation)
Patients undergo primary tumor resection and retroperitoneal lymph node sampling followed by observation. Patients who have undergone prior surgery without nodal sampling undergo observation only.
干预措施: Conventional Surgery (Procedure)
Stratum II (exploratory surgery, observation)
Patients undergo primary tumor resection and extended regional lymph node dissection followed by observation. Patients who have undergone prior surgery with simple resection of the primary tumor undergo exploratory surgery with extended regional lymph node dissection followed by observation.
干预措施: Conventional Surgery (Procedure)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Cisplatin (Drug)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Conventional Surgery (Procedure)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Doxorubicin Hydrochloride (Drug)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Etoposide (Drug)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Filgrastim (Biological)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Mitotane (Drug)
Stratum III (chemotherapy, surgery)
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
干预措施: Pegfilgrastim (Biological)
结局指标
主要结局
Five Year Event-free Survival (EFS)
时间窗: Up to five years after enrollment
The model used for comparison will be an exponential model with a constant failure rate of 0.053 (stratum I), 0.347 (stratum II), 0.602 (stratum III and IV) per year for the first two years and 0 after that. The one-sample one-sided log-rank test comparing the observed data with the hypothesized model (Woolson, 1981) of size 0.05 will be used to assess whether the data are consistent with the target models. Since this test has independent increments, the method of Lan and DeMets will be used to derive the p-values for testing procedure.
次要结局
- Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin.(Patients who had surgery at time of enrollment.)
- Frequency of Tumor Spillage at the Time of Tumor Resection(Up to one year or while on protocol therapy, whichever is less)
- Incidence and Type of Germline TP53 Mutations in Non-Brazilian Children and Children From Southern Brazil by Deoxyribonucleic Acid (DNA) Sequencing and Affymetrix Gene Chip Analysis.(At study enrollment)
- Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(Up to 182 Days After Enrollment)
- Frequency of Lymph Node Involvement by Imaging.(At study enrollment)
- Complications Associated With Radical Adrenalectomy and RLND(Up to 1 month after surgery)