A Phase I/II Dose Intensification Study Using Three Dimensional Conformal Radiation Therapy And Concurrent Chemotherapy For Patients With Inoperable, Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 41
- 主要终点
- Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them with specialized radiation therapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the effectiveness of radiation therapy combined with paclitaxel and carboplatin in treating patients who have stage III non-small cell lung cancer.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of 3-dimensional conformal radiotherapy when administered concurrently with paclitaxel and carboplatin in patients with inoperable stage IIIA or IIIB non-small cell lung cancer. (Phase I) (Closed to accrual as of 01/13/04.)
- Determine the 12-month survival rate in patients treated with this regimen. (Phase II) (Closed to accrual as of 11/27/07.)
- Determine the toxicity of this regimen in these patients.
- Determine the partial organ tolerance doses for the lung and esophagus in patients treated with this regimen.
- Determine the complete response rate in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of 3-dimensional conformal radiotherapy.
- Phase I (closed to accrual as of 01/13/04): Patients undergo 3-dimensional conformal radiotherapy once daily five days a week for 7-8 weeks. Patients also receive concurrent chemotherapy comprising paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43.
Cohorts of 7-9 patients receive de-escalating doses of 3-dimensional conformal radiotherapy until the maximum tolerated dose (MTD) is determined when given in combination with chemotherapy. The MTD is defined as the highest dose at which no more than 1 patient experiences dose-limiting toxicity.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I: 75.25 Gy/36 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: carboplatin (Drug)
Phase I: 75.25 Gy/36 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: paclitaxel (Drug)
Phase I: 75.25 Gy/36 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: three-dimensional conformal radiation therapy (Radiation)
Phase I: 74 Gy/37 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: carboplatin (Drug)
Phase I: 74 Gy/37 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: paclitaxel (Drug)
Phase I: 74 Gy/37 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: three-dimensional conformal radiation therapy (Radiation)
Phase I: 70 Gy/35 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: carboplatin (Drug)
Phase I: 70 Gy/35 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: paclitaxel (Drug)
Phase I: 70 Gy/35 fx + chemotherapy
Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: three-dimensional conformal radiation therapy (Radiation)
Phase II: 74 Gy/37 fx + chemotherapy
Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: carboplatin (Drug)
Phase II: 74 Gy/37 fx + chemotherapy
Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: paclitaxel (Drug)
Phase II: 74 Gy/37 fx + chemotherapy
Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
干预措施: three-dimensional conformal radiation therapy (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy
时间窗: From start of treatment to 90 days
Dose limiting toxicity (DLT) = Grade 3/4 non-hematologic toxicities (excluding nausea, vomiting, and alopecia) and Grade 4 hematologic toxicities. The DLT rate for this study was set at 40% based on Radiation Therapy Oncology Group (RTOG) study 94-10. No acute (within 90 days from start of 3DRT) DLT's in the first 5 patients (0/5) or the combination of one acute DLT in the first 5 patients (1/5) and none in the next 2 patients (0/2) was required to deem a given dose level to be acceptable. If at any time a Grade 5 toxicity (death) occurred, accrual would be suspended and the event reviewed by a study chair. At any given dose level, this design gives at least 90% confidence that the true acute DLT rate is less than 40% and the probability of not escalating when the true toxicity rate is 40% or higher is at least 83%. Rating scale: 0 = not the MTD, 1 = MTD
Percentage of Patients Who Survive at Least 12 Months
时间窗: From registration to 1 year
Null hypothesis: p\<= 62.3% (the best arm of RTOG 94-10); alternative hypothesis: p\>= 77.9%. Where p is the percentage of patients alive at at 12 months. Using a one-group chi-square test with alpha = 0.10, a sample size of 50 patients provides at least 87% power to detect a 25% or greater relative increase in the 12-month survival rate, or equivalently, an absolute increase of at least 15.6 percentage points (62.3 versus 77.9). If the point estimate is greater than 71.1% (upper bound), then the conclusion is that the 12-month survival rate from the new treatment significantly improved from 62.3%.
次要结局
- Number of Patients With Complete Response at 3 Months After Completion of Therapy(From start of treatment until 3 months after completion of all study treatment, estimated to be 5 or 6.5 months depending whether or not subject received optional adjuvant chemotherapy.)
- Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities.(Chemotherapy/Acute RT toxicity: from start of treatment to 90 days from start of study treatment; Late RT toxicity: from 90 days after start of treatment to last follow-up (Maximum follow-up = 57.9 months.))
- Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level)(From start of treatment to last follow-up (Maximum follow-up = 57.9 months.))
- Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level)(From start of treatment to last follow-up (Maximum follow-up = 57.9 months.))