Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 58
- 主要终点
- (Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD)
研究概览
简要总结
RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.
PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with stage I non-small cell lung cancer.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I)
- To estimate the local control rate of SBRT at the MTD in these patients. (Phase II)
Secondary
- To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients.
- To estimate the rates of late adverse events (i.e., occurs > 1 year after the start of SBRT) in these patients.
- To estimate the local control and progression-free and overall survival rates in patients treated with this regimen.
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
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
- •Stage T1-2, N0, M0 disease
- •Tumor size ≤ 5 cm
- •Tumor must be within or touching the zone of the proximal bronchial tree, defined as a volume of 2 cm in all directions around the proximal bronchial tree (i.e., carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right, and left lower lobe bronchi) OR immediately adjacent to the mediastinal or pericardial pleura (PTV touching the pleura)
- •Hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan are considered N0
- •Mediastinal lymph node sampling by any technique is allowed but not required
- •Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan or abnormal PET scan (including suspicious but nondiagnostic uptake) are eligible provided directed tissue biopsies of all abnormally identified areas are negative for cancer
- •Tumor deemed technically resectable, in the opinion of an experienced thoracic cancer surgeon, with a reasonable possibility of obtaining a gross total resection with negative margins, defined as a potentially curative resection (PCR)
- •Patient deemed "medically inoperable" due to severe underlying physiological medical problems that would prohibit a PCR, including any of the following:
- •Baseline forced expiratory volume at one second (FEV1) < 40% predicted
- •Postoperative FEV1 < 30% predicted
- •Severely reduced diffusion capacity
- •Baseline hypoxemia and/or hypercapnia
- •Exercise oxygen consumption < 50% predicted
- •Severe pulmonary hypertension
- •Diabetes mellitus with severe end-stage organ damage
- •Severe cerebral, cardiac, or peripheral vascular disease
- •Severe chronic heart disease
- •Measurable disease as documented by CT scan or whole-body PET scan within the past 8 weeks
- •Patients with lesions that cannot be visualized by CT scan are not eligible
- •Pleural effusion allowed provided it is deemed too small to tap under CT guidance and is not evident on chest x-ray
- •Pleural effusion that appears on chest x-ray is allowed only after thoracotomy or other invasive procedure
- •PATIENT CHARACTERISTICS:
- •Zubrod performance status 0-2
- •Not pregnant
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 60 days after completion of study therapy
- •No other invasive malignancy within the past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
- •Prior lung cancer allowed provided the patient has been disease-free for ≥ 2 years
- •PRIOR CONCURRENT THERAPY:
- •No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
- •No prior chemotherapy for the study cancer
- •No other concurrent local therapy (including standard-fractionated radiotherapy and/or surgery) or systemic therapy (including standard chemotherapy or biologic targeted agents) specifically intended as treatment for study cancer
- •Local or systemic therapy at the time of disease progression allowed
排除标准
- 未提供
研究组 & 干预措施
Level 9: 12.0 Gy/FX
SBRT 60.0 Gy
干预措施: SBRT 60.0 Gy (Radiation)
Level 8: 11.5 Gy/FX
SBRT 57.5 Gy
干预措施: SBRT 57.5 Gy (Radiation)
Level 3: 9.0 Gy/FX
SBRT 45.0 Gy
干预措施: SBRT 45.0 Gy (Radiation)
Level 4: 9.5 Gy/FX
SBRT 47.5 Gy
干预措施: SBRT 47.5 Gy (Radiation)
Level 5: 10.0 Gy/FX
SBRT 50.0 Gy
干预措施: SBRT 50.0 Gy (Radiation)
Level 6: 10.5 Gy/FX
SBRT 52.5 Gy
干预措施: SBRT 52.5 Gy (Radiation)
Level 7: 11.0 Gy/FX
SBRT 55.0 Gy
干预措施: SBRT 55.0 Gy (Radiation)
Level 1: 8.0 Gy/FX
SBRT 40.0 Gy
干预措施: SBRT 40.0 Gy (Radiation)
Level 2: 8.5 Gy/FX
SBRT 42.5 Gy
干预措施: SBRT 42.5 Gy (Radiation)
结局指标
主要结局
(Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD)
时间窗: From start of SBRT to 2 years.
Primary tumor control is defined as the absence of primary tumor failure. Primary tumor failure (PTF) refers to the primary treated tumor after protocol therapy and corresponds to meeting following two criteria: 1) Increase in tumor dimension of 20% as defined above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE should be avid on Positron Emission Tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, OR the measurable tumor should be biopsied confirming viable carcinoma. Marginal Failures (MF) and Involved Lobe Failures were also counted as PTF. The cumulative incidence method was used to estimate primary tumor control rate. The 90% confidence interval for local control was calculated using bootstrapping methods. Per the protocol, only the MTD dose level was to be analyzed. However, due to the quantity of patients enrolled on Dose Level 8 as well as safety concerns, Dose Level 8 was analyzed also.
(Phase I) Maximum Tolerated Dose of Stereotactic Body Radiotherapy (SBRT) as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0
时间窗: From start of SBRT to 1 year
Maximum tolerated dose (MTD) defined as dose most closely associated with a 20% probability of experiencing a toxicity \<= 1 year from start of SBRT from following dose-limiting toxicities: Gr 3-5 Cardiac: Pericardial effusion, Pericarditis, Restrictive cardiomyopathy; Gr 4-5 GI: Dysphagia, Esophagitis, Esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage; Gr 3-5 Nervous System Disorders: Brachial plexopathy, Recurrent laryngeal nerve palsy, Myelitis; Gr 3-5 Respiratory: Atelectasis (gr 4-5 only), Bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, Bronchial/pulmonary/bronchopleural/tracheal fistula, Hypoxia (provided gr 3 is worse than baseline), Bronchial/tracheal obstruction, Pleural effusion, Pneumonitis, Pulmonary fibrosis; Changes in Pulmonary Function Tests per SBRT Pulmonary Toxicity Scale, Gr 3-5: FEV1 decline, FVC decline; Any Gr 5 adverse event attributed to treatment. Dose level was determined by time-to-event continual reassessment method (TITE-CRM).
次要结局
- Rate of Toxicity ≥ Grade 3 (Other Than DLT) Within One Year as Assessed by NCI CTCAE v4.0(From start of SBRT until 1 year.)
- Progression-free Survival(From randomization to date of death, failure (local, regional or distant) or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.)
- Overall Survival(From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.)
- Rate of Late Toxicity (i.e., Occurs > 1 Year After the Start of SBRT) of ≥ Grade 3 as Assessed by NCI CTCAE v4.0(From start of treatment to end of follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.)
- Nodal Progression(From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.)
- Local Progression(From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months.)
- Distant Metastases(From randomization to date of death, distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.)