Sequential High-Dose Chemotherapy Combining Two Mobilization and Cyto-Reductive Treatments Followed by Three High-Dose Chemotherapy Regimens Supported by Autologous Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Complete response rate
研究概览
简要总结
High-dose chemotherapy (HD-CT) is able to circumvent platinum-resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach.
Patients with relapsed (but not absolutely refractory to Cisplatinum-based chemotherapy) poor-prognosis GCTs are scheduled to receive 2 cycles combining epirubicin and paclitaxel followed by 3 consecutive HD-CT supported by stem cell transplantation. One course will combine Taxol, 360 mg/m² + thiotepa, 720 mg/m², followed by two ICE regimens (Ifosfamide, 12 g/m², carboplatin, AUC 20, etoposide, 1500 mg/m²).
This phase II study is designed as a Gehan method. The main objective of the study is the complete response rate. With this aim in view, it is planned to enroll in its first step 14 patients to insure that if no complete response (CR) is noticed, study would be stopped for inefficacy (i.e., a CR rate lower than 20%). If one or more CR are noticed, protocol specified that up to 45 patients will be included in order to reduce the confidence interval (CI) of the CR rate. Secondary objectives are the overall response rate (RR), the overall survival (OS) and the progression-free survival (PFS) rates, toxicity and toxic death rate. The statistical analysis is done in terms of intent-to-treat.
详细描述
The treatment is designed for relapsed poor prognosis patients with testicular or extra-gonadal GCTs previously treated with cisplatin-containing regimens.
Poor prognosis patients are defined as either relapsed/refractory patients more than one month after cisplatin administration, whether in the course of first-line CT or in that of salvage treatment, or patients who showed evidence of progression after at least 2 lines of cisplatin-containing CT (i.e., BEP and VeIP).
Eligibility requirements includes the following criteria: age >18 years and < 65, performance status < 3, histologically or biologically documented GCTs, testicular, abdominal or mediastinal tumors, measurable or evaluable disease, life expectancy > 3 months, normal cardiac, liver, and renal function tests, absence of infection, HIV negative test, and signed informed consent. All patients had to have been previously treated with at least one line of a cisplatin-containing regimen and were included if they were refractory after one or two line(s) of cisplatin-based CT, or had relapsed after two lines of a cisplatin-based CT.
Non-inclusion criteria are: patients with 'BEYER' score > 3, growing teratoma syndrome, possibility of being treated with a conventional cisplatin-based CT, and previous HD-CT regimen.
During the initial evaluation: each patient must have a clinical evaluation that includes measurements of tumor marker levels, and an imaging work up. The tumor marker levels are determined every week during all the sequence of treatment (normal level < 10 ng/ml for alpha-foetoprotein and < 2 mU/mL for HCG). The tumor mass is measured after the first two cycles of induction/mobilization therapy and at the end of the treatment.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Eligibility requirements includes the following criteria:
- •Age >18 years and < 65
- •Performance status < 3
- •Histologically or biologically documented GCTs
- •Testicular, abdominal, or mediastinal tumors
- •Measurable or evaluable disease
- •Life expectancy > 3 months
- •Normal cardiac, liver, and renal function tests
- •Absence of infection
- •HIV negative test
- •Signed informed consent
- •All patients had to have been previously treated with at least one line of a cisplatin-containing regimen and were included if they were refractory after one or two line(s) of cisplatin-based CT, or had relapsed after two lines of a cisplatin-based CT
排除标准
- •Fireproof diseases (progress unless month with regard to the last cycle of chemotherapy or in the course of chemotherapy)
- •Relapses after complete answer obtained by surgery ( sCR )
- •Neuropathy of superior rank or = II - renal Function (Office) superior creatinine or = 125 mmol/l and/or clearance of the creatinine subordinate or = II 60ml / mn
- •Antecedents of congestive even compensated cardiac insufficiency
- •Hurts of growing teratoma that is measurable hurts increasing by size (cutting) in the absence of rise of marker pens
- •Extensive chemotherapy with support of haematopoietic stem cells. NB: A previous preventive irradiation under diaphragmatitis for a seminoma stage I (dose from 24 to 30 Gy in classic spreading) does not establish one against formal indication. However, an estimation clarifies capacities of the haematopoietic marrow is recommended with observation of the evolution of the NFP in the course of chemotherapy and quantification of cells CD 34 + in the peripheral blood. It's the same of the case where a chemotherapy by carboplatine was realized
研究组 & 干预措施
1
1
干预措施: paclitaxel (Drug)
1
1
干预措施: etoposide (Drug)
1
1
干预措施: high-dose and autologous stem cell transplantation (Procedure)
1
1
干预措施: epirubicin (Drug)
1
1
干预措施: ifosfamide (Drug)
1
1
干预措施: carboplatin (Drug)
结局指标
主要结局
Complete response rate
时间窗: during de study
Complete response rate
次要结局
- Survival (overall and progression-free), toxicity, toxic-death rate.(during the study)