Description:
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.
Title
- Brief Title: Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer
- Official Title: A Randomized Phase III Trial of Induction/Consolidation Atezolizumab (NSC #783608) + SBRT Versus SBRT Alone in High Risk, Early Stage NSCLC
Clinical Trial IDs
- ORG STUDY ID:
NCI-2019-08627
- SECONDARY ID:
NCI-2019-08627
- SECONDARY ID:
S1914
- SECONDARY ID:
S1914
- SECONDARY ID:
U10CA180888
- NCT ID:
NCT04214262
Conditions
- Lung Non-Small Cell Carcinoma
- Stage I Lung Cancer AJCC v8
- Stage IA1 Lung Cancer AJCC v8
- Stage IA2 Lung Cancer AJCC v8
- Stage IA3 Lung Cancer AJCC v8
- Stage IB Lung Cancer AJCC v8
- Stage IIA Lung Cancer AJCC v8
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq | Arm A (atezolizumab, SBRT) |
Purpose
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.
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A (atezolizumab, SBRT) | Experimental | Patients receive atezolizumab 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 (SBRT) | Active Comparator | Beginning 21 days after randomization, patients undergo SBRT for 3-5 treatments over 1-3 weeks. | |
Eligibility 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 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 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 < 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
- 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
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall survival |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Will compare overall survival between patients with inoperable, T1, T2, limited T3, N0M0 (early stage) non-small cell lung cancer randomized to stereotactic body radiation therapy with or without atezolizumab. Will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression model and estimated using a stratified Cox regression model. |
Secondary Outcome Measures
Measure: | Progression free survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression model and estimated using a stratified Cox regression model. |
Measure: | Incidence of adverse events |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | National Cancer Institute (NCI) |
Last Updated
August 30, 2021