Clinical Trials /

A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC

NCT02314364

Description:

This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS proto-oncogene 1 (ROS1) gene (= oncogene-driven NSCLC) and for which the subject has been receiving treatment with a targeted biological agent such as erlotinib, crizotinib, or other drugs.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC
  • Official Title: A Phase II Trial of Integrating Stereotactic Body Radiation Therapy With Selective Targeted Therapy in Stage IV Oncogene-driven Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 14-370
  • NCT ID: NCT02314364

Conditions

  • Non-small Cell Lung Cancer Metastatic
  • Targetable Oncogenes (EGFR, ALK, ROS1)

Purpose

This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS proto-oncogene 1 (ROS1) gene (= oncogene-driven NSCLC) and for which the subject has been receiving treatment with a targeted biological agent such as erlotinib, crizotinib, or other drugs.

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. The investigational intervention in this study is SBRT with
      proton or photon radiation (explained below). "Investigational" means that the intervention
      is being studied. SBRT and proton radiation therapy are FDA approved radiation delivery
      systems. However, using it as a treatment for stage IV NSCLC is still investigational.

      SBRT is a specialized, technologically advanced type of external beam radiation therapy that
      pinpoints high doses of radiation directly on the cancer. Because of high precision, these
      treatments spare healthy tissue and are associated with fewer side effects. SBRT is very
      different from conventional therapy where radiation is delivered in small doses given daily
      over the course of several weeks. For SBRT, the total dose of radiation is typically
      administered in 4-5 daily sessions. SBRT can be delivered with standard, so called photon
      radiation, or proton beam. Neither of these two types of radiation is generally superior over
      the other. There are technical differences between these two, and depending on tumor
      location, size, shape, and other factors, the investigators will decide which type of
      radiation to use for which treatment.

      After the screening procedures confirm you are eligible to participate in the research study:

      - Each participant will receive stereotactic treatment course (SBRT with protons or photons)
      to the area of their tumor.
    

Trial Arms

NameTypeDescriptionInterventions
SBRT with protons or photonsExperimentalDosage determined by treating physician If there is more than one active site of cancer, additional site(s) will be treated with stereotactic treatment courses. The total duration of SBRT courses (from the first day of any SBRT course to the last day of any SBRT course) will not exceed 4 months.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with any
                 actionable mutation or translocation in EGFR, ALK, or ROS1
    
              -  Stage IV disease (AJCC Staging system 7th edition)
    
              -  Within 6 months of initiating their first TKI treatment regimen
    
              -  Stable or responding systemic disease to TKI (no evidence of progression) on the most
                 recent staging studies. The complete extent of the current residual systemic disease
                 must be deemed amenable to SBRT as per review of imaging studies by a radiation
                 oncologist, based on the following criteria:
    
                   -  Lung: 1-3 lesions (including the primary) of maximum size 5 cm in longest
                      diameter. A minimum size 1 cm in the longest diameter is recommended. (Patients
                      with a malignant pleural effusion prior to the start of TKI therapy will be
                      considered eligible for SBRT if there is complete radiographic resolution of the
                      effusion while on systemic therapy);
    
                   -  Spine: Bone lesions must be limited to the spine. A maximum of 2 spinal
                      metastases will be considered for SBRT, with each site spanning 1-3 vertebral
                      bodies. A minimum size of 1 cm in longest diameter is recommended. SBRT may
                      target sclerotic lesions that persist following TKI therapy;
    
                   -  GI: 1-4 liver metastases of maximum size 5 cm in longest diameter and/or 1-2
                      adrenal metastases of maximum 4 cm size in longest diameter. A minimum size of 1
                      cm in longest diameter is recommended.
    
            In addition:
    
              -  CNS: 1-4 brain metastases of maximum size 3cm in longest diameter. However, these
                 should be treated with standard-of-care SRS and will not be defined as target lesions
                 for purposes of this protocol.
    
              -  A maximum number of 5 target lesions outside the brain, excluding the lung primary, is
                 recommended to ensure that enrollment is limited to patients with low-burden disease
                 and that treatments can be delivered within the specified time frame.
    
                   -  History of prior radiation therapy to brain or skeleton is allowed, but should
                      have occurred > 2 months from enrollment.
    
                   -  Age at least 18 years.
    
                   -  Life expectancy of greater than 6 months.
    
                   -  ECOG performance status ≤ 2.
    
                   -  Women of child-bearing potential and men must agree to use adequate contraception
                      (hormonal or barrier method of birth control; abstinence) prior to study entry
                      and for the duration of study participation. Should a woman become pregnant or
                      suspect she is pregnant while participating in this study, she should inform her
                      treating physician immediately. A negative serum or urine pregnancy test within 2
                      weeks of registration for women of childbearing potential is required.
    
                   -  Ability to understand and the willingness to sign a written informed consent
                      document.
    
            Exclusion Criteria:
    
              -  Residual hilar or mediastinal lymph node disease (size > 1cm in short-axis diameter on
                 CT). Non-malignant etiologies for enlarged lymph nodes may be evaluated per standard
                 clinical practice.
    
              -  Participants who have received prior radiation therapy to anatomical sites other than
                 brain or skeleton.
    
              -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, or psychiatric illness/social situations that would limit compliance with
                 study requirements.
    
              -  Patients who are pacemaker or defibrillator-dependent as these devices may not be
                 operated concurrently with delivery of proton beam radiation.
    
              -  Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
                 or fetus.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Frequency of distant failures (DF) after SBRT
    Time Frame:12 months
    Safety Issue:
    Description:To analyze frequency of patients with DF (with or without concurrent original site failure) in oncogene-driven NSCLC patients with residual oligometastatic disease at 12 months after initiation of SBRT

    Secondary Outcome Measures

    Measure:Number of Participants with Adverse Events
    Time Frame:Up to 2 years
    Safety Issue:
    Description:To describe toxicities of treatment using CTCAE v4.0
    Measure:Progression Free Survival
    Time Frame:Duration of time from documented start of TKI therapy to time of progressive disease, assessed up to 5 years.
    Safety Issue:
    Description:To analyze median progression free survival time
    Measure:Overall Survival
    Time Frame:Duration of time from the start of documented TKI therapy for up to 5 years or until time of death, whichever occurs first.
    Safety Issue:
    Description:To analyze median survival time and 2-year overall survival rate
    Measure:Pattern of original and distant site failures (OF and DF)
    Time Frame:2 Years
    Safety Issue:
    Description:
    Measure:Local control of lesions treated with SBRT
    Time Frame:The duration of LC is defined as the time period between the completion of SBRT to the time of objective progressive disease, assessed up to 5 years.
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Massachusetts General Hospital

    Trial Keywords

    • Non-small cell lung cancer
    • Metastatic
    • EGFR
    • ALK
    • ROS1
    • Stereotactic Body Radiation Therapy

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