Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer
Purpose
This phase III 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.
Conditions
- Lung Non-Small Cell Carcinoma
- Stage I Lung Cancer AJCC v8
- Stage II Lung Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
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 pericardial
involvement. Patients with multifocal tumors with no more than two lesions confirmed
or suspected to be synchronous early stage NSCLCs are eligible provided at least one
lesion is histologically or cytologically proven to be NSCLC and meets one or more
high-risk features
- Disease must have one or more of the following high-risk features:
- Tumor diameter >= 2 cm (inclusive of any non-solid, ground glass component) as
assessed by diagnostic CT
- Tumor standard uptake value (SUV) max >= 6.2 as assessed by FDG PET/CT
- Moderately differentiated, poorly differentiated, or undifferentiated histology
- Patient must have undergone diagnostic chest CT with or without contrast (IV contrast
preferred) within 42 days prior to randomization. PET-CT may be used if the CT portion
is of comparable 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. For cases in which the treating physician/multidisciplinary opinion is used
to define nodes as "non-suspicious" (such as long-standing, stable enlarged nodes from
other medical causes), the rationale must be clearly documented within the medical
record
- 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 the current NSCLC diagnosis
- Patient must not have undergone prior radiation to overlapping regions of the chest
that, in the opinion of the treatment physician, will interfere with protocol
treatment
- 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 (LVEF) < 40% within 28
days prior to randomization
- NOTE: Assessment of LVEF by echocardiogram or multigated acquisition (MUGA) is
not an eligibility requirement, but if a standard of care echocardiogram or MUGA
was clinically indicated, the LVEF must not be < 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 ribonucleic acid (RNA) test
- Patient must have pulmonary function testing to include, at a minimum, forced
expiratory volume in 1 second (FEV1) and Diffusing capability of carbon monoxide
(DLCO) documented within 90 days prior to randomization
- Patients with known human immunodeficiency virus (HIV) infection must be receiving
anti-retroviral therapy and have an undetectable viral load at their most recent viral
load test 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
- Patients must not have a prior or concurrent malignancy whose natural history or
treatment has the potential (in the opinion of the treating physician) to interfere
with the safety or efficacy assessment of the investigational regimen
- 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
- Patients of reproductive potential must have a negative serum pregnancy test within 14
days prior to randomization
- Patients must not have known active tuberculosis
- Patients must not have received a live, attenuated vaccine within 28 days prior to
randomization
- NOTE: All coronavirus disease 2019 (COVID-19) vaccines that have received Food
and Drug Administration (FDA) approval or FDA emergency use authorization are
acceptable
- Patients must not have a known history of allergic reactions attributed to compounds
of similar chemical or biologic composition to atezolizumab
- Patients must not have a known history of severe allergic, anaphylactic, or other
hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster
ovary cell products or to any component of the atezolizumab formulation
- 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
- Patients who can complete quality of life instruments in English, French, or Spanish
must agree to complete the questionnaires at the protocol-specified time points
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A (atezolizumab, SBRT) |
Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 1 cycle 3, patients also undergo SBRT for 3-8 treatments every 2 days or QD over 1-3 weeks. Patients undergo FDG-PET/CT during screening. Patients undergo blood sample collection and CT scans throughout the trial. |
|
|
Active Comparator Arm B (SBRT) |
Beginning 21 days after randomization, patients undergo SBRT for 3-8 treatments every 2 days or QD over 1-3 weeks. Patients undergo FDG-PET/CT during screening. Patients undergo blood sample collection and CT scans throughout the trial. |
|
Recruiting Locations
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More Details
- NCT ID
- NCT04214262
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
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. HEALTH-RELATED QUALITY OF LIFE (HRQOL) OBJECTIVE: I. To assess quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ)-30 and EORTC-QLQ- Lung Cancer (LC)13 between the arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 1 cycle 3, patients also undergo SBRT for 3-8 treatments every 2 days or once daily (QD) over 1-3 weeks. Patients undergo fludeoxyglucose F-18 (FDG)-positron emission tomography/computed tomography (PET/CT) during screening. Patients undergo blood sample collection and CT scans throughout the trial. ARM B: Beginning 21 days after randomization, patients undergo SBRT for 3-8 treatments every 2 days or QD over 1-3 weeks. Patients undergo FDG-PET/CT during screening. Patients undergo blood sample collection and CT scans throughout the trial. After completion of study treatment, patients are followed for 5 years after randomization.