Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer
Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer
This trial studies how well atezolizumab added to the usual radiation therapy works in
 treating patients with stage I-IIA non-small cell lung cancer. Immunotherapy with monoclonal
 antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and
 may interfere with the ability of tumor cells to grow and spread. Radiation therapy, such as
 stereotactic body radiation therapy, uses special equipment to position a patient and deliver
 radiation to tumors with high precision. This method can kill tumor cells with fewer doses
 over a shorter period and cause less damage to normal tissue. Giving atezolizumab and
 radiation therapy may work better than radiation therapy alone in treating patients with
 early non-small cell lung cancer.
PRIMARY OBJECTIVE:

 I. To compare overall survival (OS) in patients with inoperable, early stage non-small cell
 lung cancer (NSCLC) randomized to stereotactic body radiation therapy (SBRT) with or without
 atezolizumab.

 SECONDARY OBJECTIVES:

 I. To compare investigator-assessed progression-free survival (IA-PFS) between the arms.

 II. To compare progression free survival (PFS) by blinded independent centralized review
 (BIRC) between the arms in a random subset of patients.

 III. To evaluate distant, locoregional, and local failure rates within each treatment arm.

 IV. To evaluate the frequency and severity of toxicities within each treatment arm.

 ADDITIONAL OBJECTIVE:

 I. To collect specimens for banking.

 OUTLINE: Patients are randomized to 1 of 2 arms.

 ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1.
 Treatment repeats every 21 days for 8 cycles. Starting on day 1 cycle 3, patients also
 undergo SBRT for 3-5 treatments over 1-3 weeks.

 ARM B: Beginning 21 days after randomization, patients undergo SBRT for 3-5 treatments over
 1-3 weeks.

 After completion of study treatment, patients are followed up at weeks 18, 30, 42, and 54,
 every 6 months for 2 years, and then every 12 months for 2 years.
Inclusion Criteria:

 -  Patient must have histologically or cytologically proven stage I-IIA or limited T3N0M0
 non-small cell lung cancer (NSCLC), without radiographic evidence of nodal or distant
 involvement (N0M0). Patient may have T3 disease with the exclusion of multifocal
 tumors and pericardial involvement

 -  Disease must have one or more of the following high-risk features:

 -  Tumor diameter >= 2 cm as assessed by diagnostic computed tomography (CT)

 -  Tumor standard uptake value (SUV) max >= 6.2 as assessed by fludeoxyglucose F-18
 (FDG) positron emission tomography (PET)/CT

 -  Moderately differentiated, poorly differentiated, or undifferentiated histology

 -  Patient must have undergone diagnostic chest CT with contrast (unless medically
 contraindicated) within 42 days prior to randomization. PET-CT may be used if the CT
 portion is of identical diagnostic quality to a stand-alone CT. All disease must be
 assessed within 42 days prior to randomization

 -  Patient must have undergone FDG PET/CT of chest within 90 days prior to randomization

 -  Patient must not have evidence of hilar or mediastinal nodal involvement. Any patient
 with radiographically suspicious hilar or mediastinal nodes (including features such
 as non-calcified nodes with a short axis diameter > 1 cm, abnormal morphology, and/or
 elevated FDG avidity) must undergo cytologic sampling of suspicious nodes to rule out
 involvement prior to randomization. Mediastinal nodal sampling for other patients is
 optional

 -  Patient must have undergone history and physical examination within 28 days prior to
 randomization

 -  Patient must be medically or surgically inoperable as documented by a board certified
 thoracic surgeon or multi-disciplinary tumor board consensus OR patient's
 unwillingness to undergo surgical resection must be clearly documented

 -  Patient must not have received any prior treatment for NSCLC

 -  Patient must not have undergone prior radiation to overlapping regions of the chest
 (such that protocol lung constraints cannot be met with a cumulative plan)

 -  Patient must not have received treatment with systemic immunostimulatory or
 immunosuppressive agents, including corticosteroids, within 14 days prior to
 randomization

 -  Patient must be >= 18 years old

 -  Patient must have Zubrod performance status of 0-2

 -  Patient must have adequate liver function defined as aspartate aminotransferase (AST)
 and alanine aminotransferase (ALT) =< 3 x institutional upper level of normal (IULN)
 within 28 days prior to randomization

 -  Patient must have adequate renal function defined as calculated creatinine clearance
 >= 30 mL/min using the following formula. The serum creatinine value used in the
 calculation must have been collected within 28 days prior to randomization

 -  Patient must have absolute neutrophil count (ANC), platelets, and hemoglobin measured
 within 28 days prior to randomization. The purpose of these tests is to collect
 baseline values to compare with on-treatment values

 -  Patient must have thyroid-stimulating hormone (TSH) measured within 28 days prior to
 randomization. The purpose of this test is to collect baseline values to compare with
 on-treatment values

 -  Patient must not have significant cardiovascular disease (New York Heart Association
 [NYHA] class II or greater)

 -  Patient must not have myocardial infarction within 90 days prior to randomization

 -  Patient must not have unstable arrhythmias or unstable angina

 -  Patient must not have known left ventricular ejection fraction < 40% within 28 days
 prior to randomization

 -  Patient must not have had an infection >= grade 3 (Common Terminology Criteria for
 Adverse Events [CTCAE] version 5.0) within 28 days prior to randomization

 -  Patient must not have an active autoimmune disease that has required systemic
 treatment in past two years (i.e., with use of disease modifying agents,
 corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine,
 insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
 insufficiency) is not considered a form of systemic treatment and is allowed

 -  Patient must be tested for hepatitis B within 28 days prior to randomization. Patient
 must not have active (chronic or acute) hepatitis B virus (HBV) infection. Patients
 may have past or resolved HBV infection. Active HBV is defined as having a positive
 hepatitis B surface antigen (HBsAg) test. Past or resolved HBV is defined as having a
 negative HBsAG test and a positive total hepatitis B core antibody (HBcAb) test

 -  Patient must be tested for hepatitis C within 28 days prior to randomization. Patient
 must not have active hepatitis C virus (HCV) infection. Active HCV is defined as
 having a positive HCV antibody test followed by a positive HCV RNA test

 -  Patient must have an forced expiratory volume in 1 second (FEV1) >= 700 cc and a
 diffusion capacity of the lung for carbon monoxide (DLCO) >= 5.5 m/min/mmHg from
 pulmonary function testing documented within 90 days prior to randomization

 -  Patient must not have known human immunodeficiency virus (HIV) unless he/she is on
 effective anti-retroviral therapy, has had at least one viral load test within 6
 months prior to randomization, and had undetectable viral load at all viral load tests
 within 6 months prior to randomization

 -  Patient must not have a history of clinically significant interstitial lung disease or
 evidence of active pneumonitis on the screening chest CT

 -  No other prior malignancy is allowed except for the following: adequately treated
 basal cell or squamous cell skin cancer, in situ cervical cancer, localized prostate
 cancer, adequately treated stage I or II cancer from which the patient is currently in
 complete remission, or any other cancer from which the patient has been disease free
 for five years

 -  Patients must not be pregnant due to the potential teratogenic side effects of the
 protocol treatment. Women of reproductive potential and men must have agreed to use an
 effective contraception method for the duration of protocol treatment, and for 5
 months (150 days) after the last dose of atezolizumab. A woman is considered to be of
 "reproductive potential" if she has had a menses at any time in the preceding 12
 consecutive months. In addition to routine contraceptive methods, "effective
 contraception" also includes heterosexual celibacy and surgery intended to prevent
 pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
 bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
 previously celibate patient chooses to become heterosexually active during the time
 period for use of contraceptive measures outlined in the protocol, he/she is
 responsible for beginning contraceptive measures. Because there is an unknown but
 potential risk for adverse events in nursing infants secondary to treatment of the
 mother with atezolizumab, breastfeeding must be discontinued prior to randomization

 -  Patient must agree to have specimens submitted for translational medicine and banking

 -  Patients must be informed of the investigational nature of this study and must sign
 and give written informed consent in accordance with institutional and federal
 guidelines

 -  As a part of the OPEN registration process the treating institution's identity is
 provided in order to ensure that the current (within 365 days) date of institutional
 review board approval for this study has been entered in the system