Phase II Trial of Standard Platinum Doublet Chemotherapy + Various Proton Beam Therapy (PBT) Doses in Order to Determine the Optimal Dose of PBT for Unresectable Stage 2/3 Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Proportion of Participants With Progression Free Survival (PFS)
研究概览
简要总结
This randomized phase II trial studies how well platinum doublet chemotherapy and proton beam radiation therapy work in treating patients with stage II-III non-small cell lung cancer that cannot be removed by surgery (unresectable). Drugs used in chemotherapy, such as carboplatin, paclitaxel, etoposide, cisplatin, and pemetrexed work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Giving platinum doublet chemotherapy and proton beam radiation therapy may work better in treating patients with non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVE:
I. To compare the 1-year progression-free survival rates of 72 gray (Gy) and 60 Gy conventionally fractionated proton beam therapy (PBT) (as part of concurrent combined modality therapy).
SECONDARY OBJECTIVE:
I. To assess the adverse events, survival, quality of life, and patterns of failure (local regional, distant metastatic) associated with two dose levels of conventionally fractionated PBT (as part of concurrent combined modality therapy).
OUTLINE: Patients are randomized to 1 of 2 arms.
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
- •Age >= 18 years
- •Histological confirmation of non-small cell lung cancer
- •Forced expiratory volume in 1 second (FEV1) > 1.0 L
- •Unresectable or medically inoperable stage 2-3 non-small cell lung cancer (based on computed tomography/positron emission tomography [CT/PET], magnetic resonance imaging [MRI] or CT of brain, and physical exam);
- •Eligible if recurrence after surgery and now has the equivalent stage 2-3 non-small cell lung cancer (NSCLC) OR had sub totally resected stage 2-3 NSCLC
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •White blood cell (WBC) >= 3.0 x 10^9/L
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- •Hemoglobin (Hgb) >= 9 g/dl
- •Platelets (plts) > 100 x 10^9/L
- •Serum creatinine < 1.5 x upper limits of normal (ULN)
- •Serum bilirubin < 1.5 x ULN
- •Provide informed written consent
- •Willing to return to enrolling institution for follow-up for a minimum of 1 year
- •Ability to undergo potentially curative chemotherapy plus radiotherapy
排除标准
- •Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Weight loss of > 10% in the past 3 months
- •Distant metastases (M1 disease)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, lupus, usual interstitial pneumonitis (UIP), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any investigational agent, that would be considered as a treatment for the primary neoplasm
- •Active second malignancy
- •History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Received chemotherapy for lung cancer within 6 months of registration
- •Previous chest radiotherapy that would overlap with the proton field
研究组 & 干预措施
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Pemetrexed (Drug)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide (Drug)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Proton Beam Radiation Therapy (Radiation)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm A (platinum doublet chemotherapy, lower dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm C (platinum doublet chemotherapy, higher dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm C (platinum doublet chemotherapy, higher dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm C (platinum doublet chemotherapy, higher dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Proton Beam Radiation Therapy (Radiation)
Arm C (platinum doublet chemotherapy, higher dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm C (platinum doublet chemotherapy, higher dose PBT)
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Proportion of Participants With Progression Free Survival (PFS)
时间窗: From randomization to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
A Cox proportional hazards model stratified by stratification factors will be used to model PFS as a function of dose to test for an overall dose effect (a one-sided p-value \< 0.10 will be considered as significant evidence of a dose effect). Subsequently, separate Cox models stratified by stratification factors will compare PFS between 72 Gy and 60 Gy (for each, a one-sided p-value \< 0.10 will be considered as significant evidence of superiority). Kaplan Meier estimates and curves by dose level will also be generated
次要结局
- Overall Survival (OS)(From randomization to death due to any cause, assessed up to 5 years)
- Number of Participants With Adverse Events(Up to 5 years)
- Proportion of Participants With Local-regional Failure(Up to 5 years)
- Proportion of Participants With Distant Metastasis(Up to 5 years)