Comparing Standard Treatment Alone to Radiation Therapy with or without Surgery with Standard Treatment for Patients with Limited Metastatic Non-Small Cell Lung Cancer

Summary

Objectives

PRIMARY OBJECTIVES:
I. To evaluate the impact of adding LCT (local consolidative therapy) to maintenance systemic therapy versus maintenance systemic therapy alone on progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC) with no evidence of progression and limited metastatic sites after first-line systemic therapy. (Phase II)
II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on overall survival for patients with metastatic NSCLC with no evidence of progression and limited metastatic sites after first-line systemic therapy. (Phase III)

SECONDARY OBJECTIVES:
I. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on in-field local failure.
II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on the time to development of new lesions.
III. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on toxicity.
IV. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on duration of maintenance systemic therapy usage.
V. To evaluate the effect of adding LCT to systemic therapy in limited stage IV NSCLC on quality of life (QOL).
VI. To collect biospecimens and evaluate the correlation between clinical outcomes and circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I (CHEMOTHERAPY ALONE): Patients may receive on of the following regimens: pemetrexed intravenously (IV) over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes on day 1 or; gemcitabine IV over 30 minutes on days 1 and 8 or; pembrolizumab IV over 30 minutes on day 1 or; atezolizumab IV over 30-60 minutes on day 1 or; nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may opt to receive nivolumab IV over 30 minutes on days 1, 15, 29 and ipilimumab IV over 30 minutes on day 1 every 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II (SBRT AND CHEMOTHERAPY): Patients undergo LCT over 2-4 weeks. If LCT cannot be used to treat primary disease sites, patients also undergo intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3DCRT) over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients may possibly undergo surgery.

Patients undergo tumor biopsy and may undergo positron emission tomography (PET) scan during screening. Patients undergo computed tomography (CT) scan, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, then annually thereafter.