Platinum Doublet Chemotherapy and Proton Beam Radiation Therapy in Treating Patients With Stage II-III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
- Conditions
- Recurrent Lung Non-Small Cell CarcinomaStage II Lung Cancer AJCC v8Stage III Lung Cancer AJCC v8Unresectable Lung Non-Small Cell Carcinoma
- Interventions
- Radiation: Proton Beam Radiation TherapyOther: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT03132532
- Lead Sponsor
- Mayo Clinic
- Brief Summary
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.
- Detailed Description
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.
ARM A: 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.
ARM C: 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.
All patients undergo computed tomography (CT) throughout the study, magnetic resonance imaging (MRI) or CT, and positron emission tomography (PET)/CT during screening.
After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (platinum doublet chemotherapy, lower dose PBT) Etoposide 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Proton Beam Radiation Therapy 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Quality-of-Life Assessment 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Questionnaire Administration 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. Arm C (platinum doublet chemotherapy, higher dose PBT) Proton Beam Radiation Therapy 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. Arm C (platinum doublet chemotherapy, higher dose PBT) Quality-of-Life Assessment 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. Arm C (platinum doublet chemotherapy, higher dose PBT) Questionnaire Administration 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Carboplatin 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Cisplatin 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Pemetrexed 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. Arm A (platinum doublet chemotherapy, lower dose PBT) Paclitaxel 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. Arm C (platinum doublet chemotherapy, higher dose PBT) Carboplatin 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. Arm C (platinum doublet chemotherapy, higher dose PBT) Paclitaxel 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.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) 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
- Secondary Outcome Measures
Name Time Method Overall survival (OS) From randomization to death due to any cause, assessed up to 5 years Will be modeled using Cox models. Kaplan-Meier estimates and curves by dose level will also be generated. OS will again be analyzed as exploratory analysis after 50 deaths per primary pairwise comparison have occurred or after all patients have completed follow-up (whichever occurs first).
Local-regional failure Up to 5 years Defined as the time from randomization to the earliest date of documentation of local recurrence. The cumulative incidence of local failure will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).
Incidence of adverse events Up to 5 years Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns by dose level (60, 72 Gy). Additionally, the relationship of the adverse event(s) to dose level will be taken into consideration.
Distant metastasis Up to 5 years Defined as the time from randomization to the earliest date of documentation of distant metastasis. The cumulative incidence of distant metastasis will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).
Trial Locations
- Locations (2)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States