Randomized Study Comparing Two Strategies Carboplatin and Etoposide Topotecan in Patients With SCLC on the Second Row With Relapsed at Least Three Months After Initial Response to Chemotherapy With Platinum-etoposide 6 Cycles
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Benefit in terms of progression-free survival of a therapeutic strategy
研究概览
简要总结
The purpose of this study was to determine prospectively in all patients with SCLC in second line therapy that progression-free survival with the expected reintroduction of platinum / etoposide is greater progression-free survival in the standard arm (topotecan ) in patients who have relapsed at least three months after initial chemotherapy with platinum-etoposide
详细描述
Topotecan is currently the only drug approved in Europe and the United States for the treatment of second line of SCLC when the recovery first line of treatment is considered inappropriate. This raises the problem of knowing when the recovery first line of treatment should be considered appropriate. Secondly, the effectiveness of response to chemotherapy can be predicted based on the response to initial chemotherapy and the time interval after stopping first line treatment. A complete response after initial treatment and a long disease-free interval are predictors of better response to a second-line treatment. There are two groups: the said patients 'sensitive', which correspond to the first-line chemotherapy and who have relapsed at least 90 days after the first-line treatment and a group of so-called patients "Refractory" refers patients who progress in 90 days or patients who have not responded or progressed during first-line treatment. Median survival is very different depending on whether patients with so-called "sensitive" or "refractory".
When relapse occurs six months after the end of the first line chemotherapy, the usual practice is to reintroduce the first-line treatment. This is based on old studies where the number of patients included was low. If the interval of time after the first line of treatment is ≥ three months, two second-line treatment strategies are possible resumption of initial chemotherapy or topotecan. The combination of cisplatin with etoposide have shown high response rate, whatever the time of relapse. There are, however, no randomized study in the literature comparing topotecan to the reintroduction of a platinum salt associated etoposide.
This study is Randomized, multicenter, controlled, open-label, second line, 2 arms.
Arm A : Carboplatin Auc 5 J1 Etoposide 100 mg / m² / J J1 to J3 IV Arm B : topotecan 2.3 mg / m²J1 to J5 po
1 line by Etoposide Cisplatin or carboplatin etoposide Time interval between the first-line chemotherapy and relapse ≥ 90 days (the date is set at J1 of the last cycle) J-28: TDM thoracoabdominal, brain CT or MRI brain, J 7: Biology, quality of life questionnaire (Lung Cancer Symptom Scale). Assessment of tumor response every 6 weeks during chemotherapy post-chemotherapy followed 2nd line: TDM every 8 weeks until progression or death.
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
- None
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
- •Lung Cancer Small cell histologically confirmed.
- •SCLC stage IV according to the TNM classification in 2009
- •Relapse localized SCLC treated with chemoradiotherapy if they are outside the radiation field.
- •Patients who have had an objective response to first-line chemotherapy with cisplatin and etoposide or carboplatin and etoposide and have a time interval > or = 90 days between relapse and first-line chemotherapy (the date is set J1 of the last cycle)
- •At least one-dimensionally measurable disease (RECIST)
- •Age > or = 18 years
- •Weight loss <10% during the last 3 months
- •Performance status (PS) < or = 2
- •Creatinine clearance> 45 ml / min.
- •Neutrophils >1,5X10 9 / L and platelets > 100X109 / L.
- •Bilirubin < 1,5 X normal.
- •Transaminases, alkaline phosphatase < 2,5 X normal except in cases of hepatic metastases (5 X normal).
- •Informed Consent signed
- •Patients with asymptomatic brain metastases may be included
- •Prophylactic brain irradiation based on the habits of each center defined in advance
排除标准
- •Lung cancer non-small cell or mixed form (small cell / non-small cell) or absence of histological evidence
- •SCLC stage I or stage II or stage III.
- •Patients who have not had an objective response to first-line chemotherapy with cisplatin and etoposide or carboplatin and etoposide or that have a time interval < 90 days between relapse and first-line chemotherapy (the date is defined in J1 of the last cycle)
- •Serum Na < 125 mmol / L
- •Hypercalcemia despite corrective treatment
- •Brain metastases or symptomatic meningeal
- •A history of malignancy within the last 5 years with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- •Other concomitant serious medical conditions: congestive heart failure, unstable angina, significant arrhythmia or previous myocardial in the previous six months trial
- •Severe or uncontrolled systemic diseases, the investigator found incompatible with the proposed protocol
- •Neurological and psychiatric disorders prohibiting comprehension test
- •Severe infectious disease during or fever > 38 ° C
- •Peripheral neuropathy > or = grade 2
- •Any geographical or psychological condition does not allow a proper understanding and compliance with the protocol.
- •Private Patient freedom following a judicial or administrative decision
- •Pregnant woman, parturient or nursing; Women of childbearing potential and men with a woman of childbearing age must have adequate contraception for the duration of the study and up to 6 months after treatment ends.
- •Patient in an exclusion period for another Biomedical study
研究组 & 干预措施
Arm A : Carboplatin-Etoposide
Intravenous administration of Carboplatin Auc 5 at Day 1 and Intravenous administration of 100 mg / m² / of Etoposide J Day 1 to Day 3 The CT scans evaluations will be conducted during chemotherapy every 6 weeks
干预措施: Carboplatin (Drug)
Arm A : Carboplatin-Etoposide
Intravenous administration of Carboplatin Auc 5 at Day 1 and Intravenous administration of 100 mg / m² / of Etoposide J Day 1 to Day 3 The CT scans evaluations will be conducted during chemotherapy every 6 weeks
干预措施: Etoposide (Drug)
Arm A : Carboplatin-Etoposide
Intravenous administration of Carboplatin Auc 5 at Day 1 and Intravenous administration of 100 mg / m² / of Etoposide J Day 1 to Day 3 The CT scans evaluations will be conducted during chemotherapy every 6 weeks
干预措施: CT scans (Device)
Arm B : Topotecan
Per os administration of 2.3 mg / m² of Topotecan Day 1 to Day 5 The CT scans evaluations will be conducted during chemotherapy every 6 weeks
干预措施: Topotecan (Drug)
Arm B : Topotecan
Per os administration of 2.3 mg / m² of Topotecan Day 1 to Day 5 The CT scans evaluations will be conducted during chemotherapy every 6 weeks
干预措施: CT scans (Device)
结局指标
主要结局
Benefit in terms of progression-free survival of a therapeutic strategy
时间窗: 18 weeks
Determine the benefit in terms of progression-free survival of a therapeutic strategy by second-line carboplatin etoposide versus topotecan in patients who relapsed at least three months after the initial chemotherapy with platinum-etoposide.
次要结局
- Overall survival(18 weeks)
- The quality of life(18 weeks)
- Objective response rate assessed by RECIST(18 weeks)
- Name and number of with treatment-related adverse events as assessed by CTCAE v4.0".(18 weeks)