A Randomized Phase II Study of Weekly Docetaxel Plus Cisplatin Followed by Gemcitabine vs. Gemcitabine Plus Cisplatin Followed by Weekly Docetaxel in the Treatment of Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 58
- 试验地点
- 2
- 主要终点
- To evaluate the 1-year treatment failure rate of two sequential chemotherapy regimens:
研究概览
简要总结
Primary to evaluate the 1-year treatment failure rate of two sequential chemotherapy regimens:
- weekly docetaxel plus cisplatin followed by gemcitabine and
- gemcitabine plus cisplatin followed by weekly docetaxel. Study design:Prospective, multi-center, open-labelled, randomized phase II study.
详细描述
Lung cancer is the leading cause of cancer death in men and women worldwide. Shifting trends in the incidence of lung cancer closely follow the patterns of cigarette smoking, although other carcinogens have been implicated. Despite intensive over the past several decades, the 5-yr lung-cancer survival rate remains a dismal 8-14%.
Although lung cancer is not the most common cancer, as the leading cause of cancer-related deaths in men and women, it is the most deadly (American Cancer Society 2000). Lung cancer is also the leading cause of cancer deaths in Taiwan. According to the vital statistics of Department of Health in Taiwan, the incidence of lung cancer is rank of 5th. However, the rank of cancer fatality is the second and first in men and women, respectively. The mortality of lung cancer have significant increasing trend in men and women during the two-decade period. There are 6,555 persons die for lung cancer in 2001.
There is only 25% of cases resectable when diagnosed and only 15~18% of cases can be surgical removed. The postoperative recurrence rate and metastasis rate are also high for NSCLC. Chemotherapy is used primarily to palliate disease symptoms and prolong survival in patients with unresectable disease (stage IIIB and IV). However, overall survival benefit is modest.
Gemcitabine has shown good activity in NSCLC, both as a single agent and in combination with various other cytotoxic drugs (Eli Lilly and Company 1999). A number of phase I and II studies in NSCLC have shown good safety and efficacy of two-drug combinations of Gemcitabine with agents other than cisplatin, including carboplatin, paclitaxel, vinorelbine, and docetaxel (Eli Lilly and Company 1999).
Gemcitabine plus cisplatin (GC) is one of the most active regimens in the treatment fir stage IIIB/IV NSCLC patients. In phase II studies, 26-54% stage IIIB/IV NSCLC patients respond to GC treatment. Good median and 1-year survival have been consistently observed (Abratt et al, 1997; Crino et al, 1997; Einhorn, 1997; Shepherd et al, 1997) In randomized phase III studies, GC demonstrated the superior survival versus cisplatin alone (Sandler A et al. 2000), significantly higher response rate versus a three-drug combination of cisplatin, mitomycin C and ifosfamideb (Crino L et al. 1999).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Written informed consent prior to beginning specific protocol procedures including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- •2. Histologically or cytologically proven non-small cell lung carcinoma.
- •Stage IIIB or IV disease, no curative treatment available, candidate for chemotherapy.
- •4. Age > 18 years and < 75 years.
- •Performance status WHO performance status 0,
- •Previous therapy:
- •(a) Chemotherapy: None. (b) Previous radiation therapy : prior irradiation for NSCLC is permitted, however, the measurable or evaluable non-measurable disease must be completely outside the radiation portal.
- •7. Unidimentional or bidimentional measurable disease.
- •Life expectancy > 12 weeks.
- •Laboratory requirements :
- •Hematology: Neutrophils * 1.5 109/l, Platelets * 100 109/l, Hemoglobin > 10 g/dl.
- •Hepatic function : Total bilirubin < 1.5 UNL, ASAT (SGOT) and ALAT (SGPT) < 2.5 UNL, Alkaline phosphatases < 5 UNL ; except in presence of only bone metastasis and in the absence of any liver disorders. Patients with ASAT and/or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study.
- •Renal function : Creatinine < 1 UNL, and creatinine clearance should be > 60 ml/min.
- •10.Complete initial lab studies within 2 weeks prior to first infusion, imaging studies within 4 weeks prior to first infusion.
- •11.Patients must be accessible for treatment and follow-up.
排除标准
- •1.Pregnant, or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation.
- •2. Symptomatic central nervous system metastasis, patients with asymptomatic brain metastasis can be accepted if the tumor is irradiated and do not need steroid to control symptom.
- •3. Pre-existing motor or sensory neurotoxicity of a severity > grade 1 by NCIC-CTG criteria.
- •4. Other serious illness or medical condition :
- •congestive heart failure or unstable angina pectoris. High risk uncontrolled arrhythmias.
- •history of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- •active uncontrolled infection.
- •contraindication for the use of corticosteroids.
- •Past or current history of neoplasm other than non small cell lung cancer, except for curatively treated non melanoma skin cancer, in situ carcinoma of the cervix within 5 years.
- •6. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry.
- •7. Concurrent treatment with any other anti-cancer therapy.
结局指标
主要结局
To evaluate the 1-year treatment failure rate of two sequential chemotherapy regimens:
weekly docetaxel plus cisplatin followed by gemcitabine and
gemcitabine plus cisplatin followed by weekly docetaxel.
次要结局
- To evaluate the median overall time to treatment failure (TTF).
- To evaluate the overall progression free survival (PFS).
- To evaluate the overall survival of each arm.
- To evaluate the time to treatment failure for first regimen.
- To evaluate the progression free survival for first regimen.
- To evaluate the response rate for each regimen.
- To evaluate the toxicity of each arm.
- To evaluate the duration of response.