Phase I/II Trial of Image-Guided, Intensity-Modulated Photon (IMRT) or Scanning Beam Proton Therapy (IMPT) Both With Simultaneous Integrated Boost (SIB) Dose Escalation to the Gross Tumor Volume (GTV) With Concurrent Chemotherapy for Stage II/III Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 146
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) for intensity-modulated photon therapy (IMRT) (Phase I)
研究概览
简要总结
This partially randomized phase I/II trial studies the side effects and best dose of image-guided, intensity-modulated photon or proton beam radiation therapy and to see how well they work in treating patients with stage II-IIIB non-small cell lung cancer. This trial is testing a new way of delivering radiation dose when only the tumor receives dose escalation while the surrounding normal structure is kept at standard level. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator (linac). The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Proton beam radiation therapy is a type of radiation therapy that uses streams of protons (tiny particles with a positive charge) to kill tumor cells. Both methods are designed to give a higher than standard dose of treatment to the tumor and may reduce the amount of radiation damage to healthy tissue near a tumor.
详细描述
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) of image-guided intensity-modulated photon (IMRT) and proton therapy (IMPT) both with simultaneous integrated boost (SIB) dose escalation to the SIBVi (internal SIB volume; defined as the gross tumor volume with consideration of respiratory motion plus setup uncertainty margin) for patients with stage II/IIIB non-small cell lung cancer (NSCLC) receiving concurrent standard chemotherapy and proton irradiation. (Phase I) II. Assess and compare survival free of grade III treatment related toxicity and local progression-free survival from day 1 of concurrent chemoradiation for stage II-IIIB NSCLC patients treated with image-guided robustly-optimized IMPT versus (vs.) IMRT, both delivered with simultaneous integrated boost (SIB). (Phase II)
SECONDARY OBJECTIVES:
I. Determine treatment-related acute and late toxicity. II. Correlate changes in standardized uptake values (SUV) on positron emission tomography (PET) and study endpoints (toxicity, tumor response, local control).
III. Correlate changes in peripheral blood biomarkers (genes, micro-ribonucleic acid [RNA], proteins) and the study endpoints.
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
- •Pathologically proven diagnosis of unresected stage II-IIIB, or recurrent after surgical resection or stereotactic body radiation therapy (SBRT) non-small cell lung cancer
- •Suitability for concurrent chemoradiation therapy per treating physician's assessment
- •Karnofsky performance status (KPS) score >= 70
- •Weight loss < 15% in the 3 months before diagnosis
- •Prior receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed
- •Adequate lung function indicated by forced expiratory volume at 1 second (FEV1) >= 1 L is required
- •The primary tumor and/or regional lymph nodes must be evaluable radiographically
- •The gross target volume (GTV) is suitable for motion management using 4 dimensional computed tomography (4D CT), internal target volume (ITV), or respiratory gating; in addition, the target coverage and normal tissue constraints must be met as specified in protocol accounting for the respiratory motion of anatomy as a whole (not just the tumor)
- •No prior radiation to the mediastinal structures
- •Hemoglobin >= 9.0 g/dL
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Total bilirubin =< 1.5 times the upper limit of normal (ULN)
- •Alanine and aspartate transaminases (ALT and AST) =< 2.5 times the ULN (=< 5 x ULN for patients with liver involvement)
- •Creatinine =< 1.5 times ULN
- •Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of MD Anderson Cancer Center (MDACC)
排除标准
- •Prior radiotherapy to any anatomic regions that would result in overlap of radiation dose distribution to critical structures (esophagus, heart, spinal cord, brachial plexus)
- •T4 tumor with direct invasion of esophagus, spinal cord, major blood vessel, or heart
- •Pregnancy
- •Patients of childbearing potential must practice appropriate contraception
- •Patient refusal
研究组 & 干预措施
Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Image Guided Radiation Therapy (Radiation)
Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Photon Beam Radiation Therapy (Radiation)
Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Image Guided Radiation Therapy (Radiation)
Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Proton Beam Radiation Therapy (Radiation)
结局指标
主要结局
Maximum tolerated dose (MTD) for intensity-modulated photon therapy (IMRT) (Phase I)
时间窗: 90 days
Will be defined as the highest simultaneous integrated boost volume (SIBV) dose that has posterior probability of dose-limiting toxicity (DLT) =\< 30%. DLT are defined as Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 3+ acute radiation toxicity, including esophagitis, pneumonitis, and skin reaction that are definitely, or probably related to radiation treatment. Toxicities will be tabulated by dose, severity, and relationship to radiation therapy.
Survival free of grade >= 3 toxicity (with a target of at least 75%) (Phase II)
时间窗: 6 months
Local progression-free survival (75% at 6 months) d (Phase II)
时间窗: 6 months
Will be defined as tumor recurrence or progression inside or at the boundary of the volume defined by the 60 Gy (relative biological effectiveness) isodose line. A Bayesian method will be applied.
MTD for intensity-modulated proton therapy (IMPT) (Phase I)
时间窗: 90 days
Will be defined as the highest SIBV dose that has posterior probability of DLT =\< 30%. DLT are defined as CTCAE 4.0 grade 3+ acute radiation toxicity, including esophagitis, pneumonitis, and skin reaction that are definitely, or probably related to radiation treatment. Toxicities will be tabulated by dose, severity, and relationship to radiation therapy.
次要结局
- Progression-free survival (Phase II)(Up to 5 years)
- Posterior probability that the DLT rate 90 days from day 1 of radiation therapy is more than 30% (Phase II)(90 days)
- Time to local failure (Phase II)(Up to 5 years)
- Overall survival (Phase II)(Up to 5 years)
- Changes in selected biomarkers (Phase II)(Baseline to up to 5 years)
- Change in symptom burden using European Quality of Life Five Dimension [EQ-5D]) (Phase II) Survey(Up to 10 minutes)
- Change in symptom burden using MD Anderson Symptom Inventory [MDASI]-Plus Survey(Up to 10 minutes)