A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer (NSCLC)
I. To assess whether patients with unresectable local-regionally advanced non-small cell
lung cancer (NSCLC) treated with targeted agents based on molecular characteristics have a
longer progression-free survival than those treated with standard care therapy alone.
I. To evaluate response rate. II. To assess toxicity. III. To assess overall survival. IV.
To correlate clinical outcomes with tumor molecular aberrations identified from deep
sequencing of selected kinomes in patients from whom adequate baseline tissue is available.
OUTLINE: Patients are randomized to 1 of 4 treatment arms. Patients are stratified according
to mutation status.
CHEMORADIATION: In all treatment arms, patients undergo concurrent intensity modulated
radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3-D CRT) once daily
(QD) 5 days a week for 6 weeks. Patients receive 1 of 2 chemotherapy regimens based on the
discretion of the treating physician. Patients receive cisplatin intravenously (IV) over 1-2
hours on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Treatment
repeats every 4 weeks for up to 2 courses in the absence of disease progression or
unacceptable toxicity. Some patients receive paclitaxel IV on days 1, 8, 15, 22, 29, and 36
and carboplatin IV weekly during radiation therapy for 6 weeks. Two courses of consolidation
treatment will begin 4-6 weeks after completion of radiation therapy with paclitaxel IV on
days 1 and 22 and carboplatin IV on days 1 and 22 in the absence of disease progression or
ARM I (induction therapy): Patients receive erlotinib hydrochloride orally (PO) QD for up to
12 weeks. Patients achieving disease progression after 6 weeks undergo concurrent
ARM III (induction therapy): Patients receive crizotinib PO twice daily (BID) for up to 12
weeks. Patients achieving disease progression after 6 weeks undergo concurrent
ARMS II AND IV (concurrent chemoradiation): Patients receive concurrent chemotherapy with
thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month, every 3 months for
2 years, every 6 months for 3 years and then yearly thereafter.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS)
The product limit estimator developed by Kaplan and Meier will be used. Their 95% confidence intervals will be estimated. Comparisons between arms will be conducted using a log rank test.
Occurrence of local or regional progression, distant metastases, or death from any cause from the time of randomization to the occurrence of one of the failure events, whichever occurs first, assessed up to 12 months
Radiation Therapy Oncology Group
United States: Food and Drug Administration
|Radiation Therapy Oncology Group||Philadelphia, Pennsylvania 19107|