Phase III Randomized Study of Standard Versus Accelerated Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer and Poor Performance Status
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 7
- 主要终点
- Overall Survival of Standard Radiation (CFRT) Versus Accelerated, Hypofractionated, Image-guided Conformal Radiotherapy (IGRT) in Treatment of Stage II-III NSCLC in Patients With Poor Performance Status at 1 Year.
研究概览
简要总结
The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction).
详细描述
The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction). Poor performance status patients can be a heterogeneous group, with tumor-related factors, other co-morbidities, or advanced age placing patients in the category. These patients have traditionally been underrepresented in clinical trials, and thus no prospective study has evaluated the efficacy of other radiotherapy dose fractionations in these patients. One phase III trial of "poor-risk" locally advanced NSCLC (RTOG 93-04) included just over 40% Karnofsky performance status 60-70 patients and showed median survival times of 9.5 and 10.3 months with 60Gy of conventional radiation therapy alone or with recombinant β-interferon [18]. 1 year overall survival was just 44% in these patients.
This study includes randomization to two arms. Arm A (experimental arm) will include IGRT, 60 Gy in 15 fractions (3 weeks). Arm B will include conventional radiation, 60-66 Gy in 30-33 fractions (6 weeks) with optional concurrent with carboplatin/taxol .
The experimental arm dose for this trial is based on a dose escalation trial at University of Texas Southwestern evaluating the maximum tolerated dose of hypofractionated IGRT in this patient population (Phase I study IRB #072010-050). Doses were escalated from 3 Gy per fraction (total dose 45 Gy) to 4 Gy per fraction (total dose 60 Gy) and evaluation for treatment related toxicity was being performed. Critical structure dose constraints will be expressed as organ dose-volume limits, with limits formulated with the approval of the study investigators using known tolerance data, radiobiological conversion models, and norms used in current practice at academic centers [27].
Randomization Schema:
Patients will be allocated to the treatment using a randomized permuted block within strata to balance for patient factors other than institution. The stratifying variables are Zubrod performance status (2 vs. > 2) and stage (II vs. III).
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must be willing and capable to provide informed consent to participate in the protocol.
- •Patients must have appropriate staging studies identifying them as AJCC stage II or III non small cell lung cancer, (according to AJCC Staging, 6th edition; see appendix III), or recurrent non small cell lung cancer. Histologic confirmation of cancer will be required by biopsy or cytology within 6 months of study entry.
- •Patients must have the potential for benefit from local therapy (at the discretion of the investigator).
- •The patient's Zubrod performance status must be 2 or greater OR patients with Zubrod performance status 0-1 and weight loss >10% are considered eligible. In addition, patients determined to be medically unfit or refusing combined modality therapy are eligible.
- •Patients must have measurable or evaluable disease.
- •Women of childbearing potential and male participants must agree to use an effective method of contraception.
- •Patients must sign study specific informed consent prior to study entry.
- •Patients must not have plans for concurrent chemoradiation therapy.
- •Patients must complete all required pretreatment evaluations
排除标准
- •Total (aggregate) gross tumor volume > 500 cm3 (500 cc's or 0.5 Liters)
- •Prior radiotherapy to the region of the study cancer that would result in direct overlap of radiation therapy fields.
- •Chemotherapy given within one week of study registration.
- •Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
研究组 & 干预措施
Radiation Therapy
Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks
干预措施: Radiation Therapy (Radiation)
Conventional Radiation
Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
干预措施: Conventional radiation (Radiation)
结局指标
主要结局
Overall Survival of Standard Radiation (CFRT) Versus Accelerated, Hypofractionated, Image-guided Conformal Radiotherapy (IGRT) in Treatment of Stage II-III NSCLC in Patients With Poor Performance Status at 1 Year.
时间窗: 1 year
Percentage of participants with overall survival at 1 year. To compare the efficacy by overall survival of standard radiation versus accelerated, hypofractionated, image-guided conformal radiotherapy in treatment of stage II-III or recurrent NSCLC in patients with poor performance status. Overall survival time will be estimated using the Kaplan-Meier approach. The stratified log-rank test will be used to test for a statistically significant difference in survival distributions. The Cox proportional hazard regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment difference in overall survival. Unadjusted ratios and ratios adjusted for stratification variables and other covariates of interest will be computed.
次要结局
- Cost Effectiveness of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.(2 years)
- Quality Adjusted Life Survival Time of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.(20 months)
- Toxicities of Two Radiotherapy Treatment Regimens in Patients With Stage II-III Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status(60 months)
- Disease-free Survival of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.(60 months)
- Time to Local Progression of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status(60 months)
- Quality of Life of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.(6 months)
研究者
Puneeth Iyengar
Associate Vice Chair of Clinical Research
University of Texas Southwestern Medical Center