A Bayesian Randomized Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 275
- 试验地点
- 2
- 主要终点
- The Incidence and Time to Development of Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) Grade > 3 Treatment-related Pneumonitis (TRP)
研究概览
简要总结
The goal of this clinical research study is to learn if, compared with regular x-ray radiation, proton radiation reduces the risk of developing, treatment-related pneumonitis (TRP) or tumor recurrence (the tumor coming back in the irradiated area after treatment) in patients with lung cancer.
详细描述
There are 2 types of radiation treatment being used in this study. One type of treatment is proton therapy. Proton therapy is a type of radiation therapy that uses a beam of proton particles (similar to getting an x-ray) to send radiation inside the body to the tumor. The other type of treatment is Image-Guided Adaptive Photon Therapy (IGAPT). IGAPT is a therapy that uses images to help guide the delivery of photon therapy to the tumor. Both of these types of radiation treatment are believed to help doctors to give a full dose of radiation treatment to the tumor while not damaging as much of the healthy tissue around it.
Study Groups If you are found to be eligible to take part in this study, you will go through the standard radiation treatment planning procedure, called the "marking session." After the marking session, a standard photon therapy plan (called Intensity Modulated Radiation Therapy, or IMRT) and a proton plan will be developed. If the radiation oncologist thinks that both the photon and proton plans are acceptable, you will then be randomly assigned to 1 of 2 groups. Participants in Group 1 will receive photon therapy. Participants in Group 2 will receive proton therapy.
The first 20 participants will have an equal chance to be assigned to either group. After at least 20 participants have been enrolled and there has been at least 1 occurrence of pneumonitis and/or tumor recurrence in each treatment Group, the risk of pneumonitis and/or tumor recurrence in all previous participants will be evaluated for each treatment Group, and that information will be used to calculate the chances of being assigned to either Group 1 or Group 2. This calculation will be updated after each occurrence of pneumonitis and/or tumor recurrence and after each participant returns for a follow-up visit. Once these calculations are begun, everyone who joins the study from that point on will be more likely to be assigned to the treatment Group that appears to be better in terms of pneumonitis and/or tumor recurrence.
If the tumor is too large and the standard radiation treatment plan created during the marking session is found not to be acceptable, and the radiation oncologist thinks radiation treatment it is necessary, you will still remain on study and be assigned to a third group. If you are assigned to Group 3, you will receive proton or photon treatment at a lower dose level and/or reduced length of radiation.
If you are assigned to Group 2 and your insurance provider denies reimbursement, you may chose not to receive proton therapy and receive photon therapy instead. If you chose to receive photon therapy, you will be in Group 4.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically proven, unresected, locoregionally advanced NSCLC without evidence of hematogenous metastases (stage II-IIIB disease according to the 7th edition of the AJCC Staging Manual) with exception as defined by inclusion #2).
- •Patients with solitary brain metastasis without sign of progression in the brain at the time of registration will be eligible for this trial if there is clinical indication for concurrent chemoradiation to the primary disease in the lung.
- •Suitability for concurrent chemoradiation therapy per treating radiation oncologists or treating medical oncologist's: A) Karnofsky performance score of >/= 70, or ECOG 0-1 B) Unintentional weight loss </= 10% during the 3 months before study entry.
- •Receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed for this protocol.
- •Measurable disease on chest x-ray, contrast-enhanced CT, or PET scan.
- •Locoregional recurrence after surgical resection, if suitable for definitive concurrent chemoradiation is allowed for this protocol.
- •Forced expiratory volume in the first second (FEV1) >/= 1 liters.
- •Fluorodeoxyglucose (FDG) -PET scan within 3 months before registration. The pretreatment (diagnostic) PET/CT should, whenever possible, be performed together with the 4-D CT simulation. PET images acquired either at the time of simulation or acquired separately should be registered with the planning CT to assist in tumor delineation.
- •Standard pretreatment evaluations (as decided by treating radiation oncologist, medical oncologist, surgeons or pulmonologist), to include MRI or CT scan of the brain, contrast CT scan of the thorax and upper abdomen, Whole-body PET/CT, pulmonary function tests, lung and cardiac single proton emission computed tomography (SPECT), liver function tests (LFT), blood chemistry, renal function tests, and complete blood count.
- •Age >/= 18 years but </= 85 years.
- •A signed specific informed consent form before study entry.
排除标准
- •Small cell histology.
- •Prior thoracic radiotherapy to regions that would result in overlap of radiation therapy fields.
- •Pregnancy (female patients of childbearing potential must practice appropriate contraception).
- •Enrollment in a clinical trial that specifically excludes IGAPT treatment.
- •Body weight exceeds the weight limit of the treatment couch.
- •Oxygen dependent due to preexistent lung disease (COPD, emphysema, lung fibrosis).
研究组 & 干预措施
Group 1
Group 1: Photon Therapy - 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Photon Therapy (Radiation)
Group 1
Group 1: Photon Therapy - 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Paclitaxel (Drug)
Group 1
Group 1: Photon Therapy - 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Carboplatin (Drug)
Group 2
Group 2: Proton Therapy - 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Proton Therapy (Radiation)
Group 2
Group 2: Proton Therapy - 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Paclitaxel (Drug)
Group 2
Group 2: Proton Therapy - 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Carboplatin (Drug)
Group 3
Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Photon Therapy (Radiation)
Group 3
Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Proton Therapy (Radiation)
Group 3
Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Paclitaxel (Drug)
Group 3
Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Carboplatin (Drug)
Group 4
Photon Therapy - Highest practical dose (74 CGE, 66 CGE) radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Photon Therapy (Radiation)
Group 4
Photon Therapy - Highest practical dose (74 CGE, 66 CGE) radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Paclitaxel (Drug)
Group 4
Photon Therapy - Highest practical dose (74 CGE, 66 CGE) radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.
Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.
Carboplatin AUC 2 by vein 1 time each week for 7 weeks.
干预措施: Carboplatin (Drug)
结局指标
主要结局
The Incidence and Time to Development of Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) Grade > 3 Treatment-related Pneumonitis (TRP)
时间窗: From date of protocol registration until the date of first documented development of CTCAE v3.0 grade > 3 TRP or local failure, whichever occurs first, in both treatment groups, assessed up to 6 years.
The Primary Objective is assess and compare the incidence and time to development of CTCAE v3.0 grade \> 3 TRP, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. TRP will be diagnosed clinically by the treating investigator. Any questions regarding the diagnosis or grade of TRP will be resolved by the Protocol PI or by his/her designee(s). The outcomes review committee will meet to discuss each and every patient reported to have developed symptomatic TRP. The final grading of TRP will be decided by the outcomes review committee. Diagnosis of TRP included receipt of radiation that included a certain volume of normal lung, radiographic changes that suggested inflammation consistent with the radiation dose distribution within 12 months after starting chemoradiation, and symptoms attributable to TRP. Final TRP outcomes also were reviewed and approved by independent external experts.
The Incidence and Time to Development of Local Failure (LF)
时间窗: From date of protocol registration until the date of first documented development of CTCAE v3.0 grade > 3 TRP or local failure, whichever occurs first, in both treatment groups, assessed up to 6 years.
The Primary Objective is assess and compare the incidence and time to development of local failure, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. Local failure was defined as treatment failure within the planning target volume plus a # 1-cm margin. Images used to report Local failure were registered with radiation dose distribution to accurately assess the location of the failure. Biopsy to confirm Local failure was strongly recommended (Data Supplement). An internal outcomes review committee reviewed each event to ensure objectivity and consistency in reporting Local failure. Final RP outcomes also were reviewed and approved by independent external experts. 1. Tumor recurrence after achieving complete response, 2. Residual tumor enlargement of 20% or more on CT according to RECIST criteria, 3. Recurrence of PET FDG Avidity after achieving complete metabolic response, 4. Increase in FDG avidity in residual tumor, 5. Pathologically proven recurrence
次要结局
未报告次要终点