Clinical Trials /

Atezolizumab and Stereotactic Body Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer

NCT02599454

Description:

This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in treating patients with stage I non-small cell lung cancer that cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving atezolizumab together with stereotactic body radiation therapy may kill more tumor cells and be a better treatment for non-small cell lung cancer that cannot be removed by surgery.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab and Stereotactic Body Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer
  • Official Title: A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients With Inoperable Stage I Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 774542
  • SECONDARY ID: UCDCC#258
  • SECONDARY ID: ML29955
  • SECONDARY ID: UCDCC#258
  • SECONDARY ID: NCI-2015-01796
  • NCT ID: NCT02599454

Conditions

  • Stage I Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280Aatezolizumab + SBRT

Purpose

This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in treating patients with stage I non-small cell lung cancer that cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving atezolizumab together with stereotactic body radiation therapy may kill more tumor cells and be a better treatment for non-small cell lung cancer that cannot be removed by surgery.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of MPDL3280A (atezolizumab) that can be
      given with stereotactic ablative radiotherapy (SAR) (stereotactic body radiation therapy) in
      patients with inoperable stage I non-small cell lung cancer (NSCLC).

      SECONDARY OBJECTIVES:

      I. To characterize the safety profile of this regimen using CTCAE v4 (Common Toxicity
      Criteria for Adverse Events version 4).

      II. To provide preliminary efficacy data of the combination as determine by objective
      response rate and disease free survival using RECIST 1.1 (Response Evaluation Criteria for
      Solid Tumors) and Immune Related RECIST (irRECIST).

      TERTIARY OBJECTIVES:

      I. To analyze serial blood for change in cytokine signatures, fluorescence activated cell
      sorting (FACS) and immunophenotyping of peripheral blood mononuclear cells (PBMCs) and tumor
      infiltrating immune cells.

      II. To evaluate pre and post treatment tumor tissue (if available) for programmed cell
      death-ligand 1 (PD-L1) and other immune proteins in the tumor and tumor microenvironment and
      for molecular profiling in a subset of patient samples.

      III. To discover biomarkers of response from the data obtained.

      OUTLINE: This is a dose-escalation study of atezolizumab.

      DOSE ESCALATION PHASE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on
      day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or
      unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo
      4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.

      EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat
      every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48
      hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body
      radiation therapy over days 1-5 of course 3.

      After completion of study treatment, patients are followed up at 30 days, every 3 months for
      2 years, and then every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
atezolizumab + SBRTExperimentalDOSE ESCALATION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3. EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven stage I NSCLC =< 5 cm diameter

          -  One or more high-risk features identified:

               -  Tumor diameter >= 2 cm

               -  Tumor standardized uptake value maximum (SUVmax) >= 6.2

               -  Moderately, poorly differentiated or undifferentiated histology

          -  Evaluable disease per RECIST 1.1

          -  Patients must be medically or surgically inoperable as determined by a physician OR
             unwilling to undergo surgical resection

          -  All patients must have an forced expiratory volume in 1 second (FEV1) >= 700cc

          -  All patients must have a carbon monoxide diffusing capability test (DLCO) >= 5.5
             m/min/mmHg

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2

          -  Life expectancy >= 12 months

          -  Absolute neutrophil count (ANC) > 1500 cells/uL

          -  White blood cell count (WBC) > 2500/uL

          -  Lymphocyte count > 500/uL

          -  Platelet count > 100,000/uL

          -  Hemoglobin > 9 g/dL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper
             limit of normal (ULN) with alkaline phosphatase =< 2.5 x ULN OR AST and ALT =< 1.5 x
             ULN, with alkaline phosphatase > 2.5 x ULN

          -  Serum bilirubin =< 1.0 x ULN

          -  International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
             < 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for
             at least 1 week prior to enrollment)

          -  Creatinine clearance > 30 mL/min by Cockcroft-Gault formula

          -  No history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)

          -  No other active malignancy

          -  Patients with a history of autoimmune-related hypothyroidism on a stable dose of
             thyroid replacement hormone are eligible

          -  Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
             eligible

          -  Archival tumor sample available; tissue from an fine-needle aspiration (FNA) is
             allowed but tumor tissue from a core needle biopsy is preferred

          -  For female patients of childbearing potential and male patients with partners of
             childbearing potential agreement (by patient and/or partner) to use highly effective
             form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year]
             when used consistently and correctly) and to continue its use for 6 months after the
             last dose of MPDL3280A

          -  Signed informed consent

          -  Ability to comply with the protocol

        Exclusion Criteria:

          -  Uncontrolled concomitant disease

          -  Significant cardiovascular disease (New York Heart Association Class [NYHA] class II
             or greater); myocardial infarction within 3 month prior to randomization, unstable
             arrhythmias, unstable angina or a patient with a known left ventricular ejection
             fraction (LVEF) < 40%

          -  Severe infection within 4 weeks prior to enrollment

          -  Active tuberculosis

          -  Oral or IV antibiotics within 2 weeks or 5 half-lives prior to enrollment

          -  History of autoimmune disease

          -  Positive for human immunodeficiency virus (HIV), hepatitis B (hepatitis B surface
             antigen [HBsAg] reactive), or hepatitis C virus (hepatitis C virus ribonucleic acid
             [HCV RNA] [qualitative] is detected)

          -  History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing
             pneumonia

          -  Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of
             the drug, whichever is shorter, prior to enrollment

          -  Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications within past 4 weeks or 5 half-lives whichever is shorter

          -  Pregnant and/or lactating women
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:9 weeks
Safety Issue:
Description:The adverse events will be summarized as frequency, proportion of patients MTD. The exact 95% confidence interval for proportion will be categorized by type, severity, nadir or maximum values for the laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities by dose and course.

Secondary Outcome Measures

Measure:Disease free survival (DFS), assessed by RECIST 1.1 and irRECIST
Time Frame:Up to 5 years
Safety Issue:
Description:DFS will be summarized with Kaplan-Meier plots. The median DFS time will be estimated using standard life table methods.
Measure:Overall response rate (ORR), assessed by RECIST 1.1
Time Frame:Time from the start of the treatment until disease progression/recurrence, assessed up to 5 years
Safety Issue:
Description:ORR will be summarized by exact binomial confidence intervals.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Karen Kelly

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