Clinical Trials /

Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer

NCT04214262

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqArm 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.

      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

NameTypeDescriptionInterventions
Arm A (atezolizumab, SBRT)ExperimentalPatients 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.
  • Atezolizumab
Arm B (SBRT)Active ComparatorBeginning 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 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 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 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
          
    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

    April 17, 2020