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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Chemotherapy
Chemotherapy
Chemotherapy
Chemotherapy
Chemotherapy
Undergo PBT
Ancillary studies
Ancillary studies
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Proportion of Participants With Progression Free Survival (PFS)
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
Time frame: From randomization to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
Overall Survival (OS)
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).
Time frame: From randomization to death due to any cause, assessed up to 5 years
Number of Participants With Adverse Events
Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Adverse events are graded on a scale of 0-5 with 5 being worst. The number of participants with Grade 2 or higher adverse events will be reported.
Time frame: Up to 5 years
Proportion of Participants With Local-regional Failure
Defined as the proportion of participants with 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).
Time frame: Up to 5 years
Proportion of Participants With Distant Metastasis
Defined as the proportion of participants with 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).
Time frame: Up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.