3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Primary Objective:

        -  Developing Common Toxicity Criteria (CTC) 3.0 grade > 3 treatment related pneumonitis
           (TRP) or

        -  Developing local-regional recurrence among patients treated with 3D conformal radiation
           therapy (CRT) (Arm 1) or intensity modulated radiation therapy (IMRT) (Arm 2).

      Secondary Objectives:

        -  To assess and compare the time to develop CTC 3.0 grade > 3 radiation esophagitis in
           patients with non-small cell lung cancer (NSCLC) treated in arm 1 and arm 2.

        -  To investigate the association of inflammatory cytokines with the time to the
           development of radiation pneumonitis and outcomes to concurrent chemoradiation between
           arm 1 and arm 2.

        -  To investigate the association of relevant pharmacogenetics, biomarkers, and gene
           polymorphisms with the time to the development of radiation pneumonitis and treatment
           outcomes to concurrent chemoradiation between arm 1 and arm 2.

        -  To evaluate image guided adaptive radiation therapy (IGART) using weekly computed
           tomography (CT) on rail or cone beam CT in the assessment of tumor response and impact
           on treatment planning and delivery.

        -  To compare overall survival, progression-free survival, median survival time, in arm 1
           and arm 2.

        -  To evaluate the role of functional image of fluorodeoxyglucose-positron emission
           tomography (FDG-PET) in assessing and predicting the time to the development of TRP and
           tumor response.

        -  To measure and compare symptom burden over time of the treatment using MD Anderson
           Symptom Inventory (MDASI)-Lung in the 2 arms.

        -  To determine the impact of comorbid conditions on survival.
    

Detailed description: 
      TRP (treatment related pneumonitis) is an inflammation (irritated or injured tissue) of the
      lungs that occurs as a result of chemotherapy or radiation therapy. TRP occurs because both
      chemotherapy and radiation affect normal lung tissue when tumors are being treated.

      3D CRT is the current standard of care. It delivers radiation to several different angles of
      the body with center focus on the tumor(s). Because it is delivered at different angles, the
      same amount of radiation that contacts the tumor(s) also contacts normal lung tissue at each
      angle.

      IMRT is a new type of radiation therapy. It also delivers radiation to several different
      angles of the body with center focus on the tumor(s). The difference is that the amount of
      treatment at each angle is adjusted according to the shape and size of the tumor(s), which in
      turn may decrease radiation exposure to normal lung tissue at each angle. Researchers want to
      find out if intensity modulated radiation therapy (IMRT) is able to decrease the amount of
      normal lung that is affected when treating lung cancer.

      Before you can start treatment on this study, you will have "screening tests." These tests
      will help the doctor decide if you are eligible to take part in this study. You will have a
      physical exam, including measurement of your vital signs (blood pressure, heart rate,
      temperature, and breathing rate). You will have blood drawn (about 1 tablespoon) and urine
      collected for routine tests. You will be asked about any other medical problems you may have
      that could cause the development of TRP. You will have tests that include a computed
      tomography (CT) scan, positron emission tomography (PET) scan, and lung function test. A PET
      scan is a scan that will show cells that take in higher levels of a type of sugar (glucose),
      such as cancer cells. Before the scan, a small dose of a slightly radioactive form of glucose
      will be injected through a vein. The cells that take in higher amounts of glucose will show
      up better on the scan. The scanning process is quite similar to a regular CT scan. No new
      biopsy is needed; only the original biopsy will be used for this study.

      You will have 2 different single photon-emission computed tomography tests (SPECTs). You will
      have a lung single-photon emission computerized tomography (SPECT)test that will show the
      area of blood flow in the normal lung. You will have a heart single-photon emission
      computerized tomography (SPECT) test that will show the areas of blood flow in the heart. To
      perform these single-photon emission computerized tomography (SPECT) tests, you will have a
      slightly radioactive substance injected into your vein so that images can be seen of the
      blood flow in the lung and heart. This will help the study doctor try to avoid using
      radiation angles that would go through the normal blood flow area. You will also have a
      biopsy of your tumor tissue. To perform a tumor biopsy, an area of the body (where tumor is
      present) is numbed with anesthetic, and a small amount of tumor tissue is withdrawn through a
      large needle or with forceps (a tong-like instrument) during an endoscopic (viewing of body
      cavity with a special instrument) exam.

      Researchers will use the results of these tests to learn the stage (size and location) of the
      cancer to see if the tumor(s) can be treated by radiation. Women who are able to have
      children must have a blood or urine pregnancy test, which will be performed on the same blood
      or urine that was collected for routine tests. To be eligible to take part in this study, the
      pregnancy test must be negative.

      If you are found to be eligible to take part in this study, your radiation doctor will first
      conduct a planning session. You will have a CT scan of your chest, and your respiratory
      (breathing) motion will be monitored. After the scan is done, your radiation doctor will
      evaluate it and make an outline of the tumor(s) in your lung. The CT scan helps the doctor
      identify (note the difference between) the tumor(s) and the normal surrounding tissue. The
      planning session helps the radiation doctor decide the target area(s), the best angles to
      deliver the radiation, and the most effective radiation dose (which is also intended to
      decrease radiation to surrounding normal tissues) for treatment.

      If the plan for treatment is considered acceptable for you by the radiation doctor, you will
      then be randomly assigned (as in the toss of a coin) to 1 of 2 treatment groups. Participants
      in one group will receive 3D CRT. Participants in the other group will receive intensity
      modulated radiation therapy (IMRT). You will have an equal chance of being in either one of
      these groups. If you are assigned to receive intensity modulated radiation therapy (IMRT),
      the total radiation dose to the tumor(s) will be slightly higher than for participants
      receiving 3D CRT.

      If the 3D CRT plan for treatment is not considered acceptable for you (usually because of a
      large target area) by the radiation doctor, you will be treated with IMRT, with or without
      amifostine. Amifostine is a drug given as an injection to protect the normal lung and
      esophagus tissue from radiation side effects and injury. Your treating physician will decide
      if you need amifostine or not, based on the size of the tumor tissue and normal tissue in the
      radiation "field" (the area given radiation during treatment). If you need amifostine, a
      nurse will give you the injection about 30 minutes before radiation treatment. Your blood
      pressure will be checked for 15-20 minutes after injection.

      Participants on this study will be receiving standard chemotherapy given together with
      radiation therapy. The standard chemotherapy usually includes cisplatin, carboplatin,
      paclitaxel, or docetaxel. The chemotherapy is not considered the investigational part of this
      study.

      All study participants will receive standard chemotherapy, given together with radiation
      therapy. The standard chemotherapy usually includes cisplatin, carboplatin, paclitaxel,
      and/or docetaxel. Your chemotherapy doctor will explain the side effects of these
      chemotherapy drugs to you before you start receiving chemotherapy. The chemotherapy is not
      the investigational part of this clinical trial.

      Participants in each group will receive a total of 6 ½ weeks of radiation therapy (once a day
      for 5 days a week). You will not be treated on the weekends or on a national holiday. If the
      disease gets worse or you experience any intolerable side effects, you will be taken off this
      study.

      After you have completed therapy on this study, you will have follow-up visits. The study
      doctor will check how the disease responded to treatment using the same imaging scans and
      blood tests (about 1 tablespoon each time) that were performed during the screening portion
      of this study. These tests will be performed about every 3-4 months after completion of
      treatment as part of your standard of care.

      This is an investigational study. Both 3D conformal radiation therapy (CRT) and intensity
      modulated radiation therapy (IMRT) are FDA approved for the treatment of cancer. Up to 168
      patients will take part in this study. All will be enrolled at M.D. Anderson.
    

Intervention name(s): Intensity Modulated Radiation Therapy; 3-Dimensional Conformal Radiation Therapy
Intervention type(s): Procedure; Procedure
Intervention description(s): 66 Gy in 33 Daily Fractions at 2 Gy per fraction.; 66 Gy in 33 Daily Fractions at 2 Gy per fraction.
Other intervention name(s): IMRT; 3D CRT
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Non-Small Cell Lung Cancer; Lung Cancer; 3-Dimensional Conformal Radiation Therapy; Intensity Modulated Radiation Therapy; 3D CRT; IMRT; NSCLC; TRP; Treatment related pneumonitis