PRIMARY OBJECTIVE:
I. To detect an improvement in overall survival with the addition of adjuvant hemithoracic
intensity-modulated pleural radiation therapy (IMPRINT) to surgery and chemotherapy compared
to surgery and chemotherapy alone.
SECONDARY OBJECTIVES:
I. To determine local failure-free survival, distant-metastases-free survival, and
progression-free survival with the addition of adjuvant hemithoracic IMPRINT to surgery and
chemotherapy compared to surgery and chemotherapy alone.
II. To evaluate the treatment-related toxicities in both arms per Common Terminology Criteria
for Adverse Events (CTCAE) version (v)5.0.
III. To detect a clinically meaningful 10-point change in global health status mean scores at
9 months after randomization with the addition of adjuvant IMPRINT as compared to surgery and
chemotherapy alone.
EXPLORATORY OBJECTIVES:
I. To evaluate the degree of under-staging, concordant and upstaging between
centrally-reviewed clinical staging (based on positron emission tomography [PET], computed
tomography [CT] and/or magnetic resonance imaging [MRI]) and pathologic staging.
II. To identify immunologic and pathologic biomarkers as predictors of response and potential
targets for future combination trials.
III. To determine the magnitude of radiation dose escalation to gross residual disease based
on combined modality imaging and associated local control rates with dose-painting
intensity-modulated radiation therapy (IMRT).
IV. To determine the rate of R0/R1 and R2 resections, and type of procedures (extended
pleurectomy/decortication [P/D], P/D and partial pleurectomy).
V. To evaluate the trajectory of European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire Core 30 (EORTC QLQ-Q30) and lung cancer specific module (LC13)
symptoms in patients treated with IMPRINT by comparing the proportion of patients who respond
with "quite a bit" or "very much" LC13 symptoms at 9-12 months post-randomization compared to
at 3 months post-randomization.
VI. To evaluate changes in health-related quality of life, functional domains, and symptoms
over time with the addition of adjuvant IMPRINT as compared to surgery and chemotherapy
alone.
OUTLINE:
STEP 1: Patients undergo P/D then within 4 to 8 weeks receive pemetrexed intravenously (IV)
over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1. Patients may
instead receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes
on day 1 then undergo P/D within 4 to 8 weeks after chemotherapy. The order of surgery and
chemotherapy is at the discretion of the treating physician.
STEP 2: Within 4 to 8 weeks from the end of Step 1 treatment, patients are randomized to 1 of
2 arms.
ARM I: Patients receive no treatment.
ARM II: Patients undergo 25-28 fractions IMRT or pencil beam scanning (PBS) proton therapy 5
days per week over 6 weeks.
After completion of study treatment, patients are followed up every 3 months for 2 years,
then every 6 months for 3 years.