A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 302
- 试验地点
- 126
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.
详细描述
OBJECTIVES:
I. Determine whether children with newly diagnosed low- or intermediate-risk extracranial germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin, etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10).
II. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.
III. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.
IV. Determine the acute toxic effects of compressed therapy in these patients. V. Determine the long-term sequelae in patients treated with this regimen. VI. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Extracranial germ cell tumor that contains 1 of the following malignant histologies: NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible provided 1 of the 3 histologies listed above is also present in the tumor.
- •Yolk sac tumor
- •Embryonal carcinoma
- •Choriocarcinoma
- •Low-risk disease (closed to accrual as of 01/20/10)
- •Stage I gonadal tumors (ovarian and testicular)
- •Must have undergone complete surgical and radiologic staging to exclude the possibility of > stage I disease
- •Intermediate-risk disease
- •Stage II, III, or IV malignant testicular GCT
- •Stage II or III malignant ovarian GCT
- •Stage I or II malignant extragonadal GCT
- •Previously stage I gonadal patients who have relapsed on the low-risk (observation) stratum of this study(closed to accrual as of 01/20/10)
- •Patients with immature teratoma or mature teratoma who relapse with a malignant component
- •No patients with any of the following diagnoses:
- •Stage IV ovarian and stage III-IV extragonadal GCT
- •Intracranial GCT
- •Pure mature or immature teratoma, pure dysgerminoma, or seminoma
- •Patients with a non-germ cell component in their GCT (e.g., primitive neuroectodermal tumors or rhabdomyosarcoma)
- •Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known
- •If > 5 days have elapsed from the time of obtaining original markers, tumor markers must be repeated before enrollment of low-risk patients and before initiating therapy in intermediate-risk patients (the results of the repeated tumor markers do not have to be known at the time of study enrollment)
- •Must be enrolled within 6 weeks of original diagnostic surgery
- •Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:
- •≤ 0.4 mg/dL (for patients 1 to 5 months of age)
- •≤ 0.5 mg/dL (for patients 6 to 11 months of age)
- •≤ 0.6 mg/dL (for patients 1 year of age)
- •≤ 0.8 mg/dL (for patients 2 to 5 years of age)
- •≤ 1.0 mg/dL (for patients 6 to 9 years of age)
- •≤ 1.2 mg/dL (for patients 10 to 12 years of age)
- •≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
- •≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
- •≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
- •No prior chemotherapy
- •No prior radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6).
After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy.
After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.
干预措施: conventional surgery (Procedure)
Arm I
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6).
After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy.
After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.
干预措施: cisplatin (Drug)
Arm I
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6).
After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy.
After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.
干预措施: etoposide (Drug)
Arm I
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6).
After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy.
After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.
干预措施: bleomycin sulfate (Biological)
Arm I
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6).
After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy.
After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: 3 Years after enrollment
Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
Overall Survival (OS)
时间窗: 3 Years after enrollment
Percentage probability of being alive at 3 years following enrollment.
次要结局
- Days Hospitalized for Patients Who Receive Chemotherapy(Up to 126 days after the start of chemotherapy)
- Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0(Up to 126 days after the start of chemotherapy)