Intensity Modulated Radiation Therapy for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Early Phase 1

Summary: 
      BACKGROUND:

      -This study represents a progression from findings in four previous National Cancer Institute
      (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B,
      04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic
      Resonance (MR) biological images and co-register tissue in prostate cancer patients.

      OBJECTIVES:

      -The primary objective of the first portion of this study is to assess the feasibility of
      using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in
      prostate cancer. Also, if feasible, we hope optimize this technique with experience.

      ELIGIBILITY:

      -This is a study of image guided, targeted radiation therapy in patients with high risk of
      nodal metastases from prostate cancer. Patients with prostate cancer who have more than 15%
      risk of lymph node (as defined by the Partin tables) metastasis will be eligible for this
      study.

      DESIGN:

        -  On the first 10 patients, we will perform approximately 5 computed tomography (CT)
           simulations throughout the course of their therapy. On each simulation, the initial
           treatment plan will be re-run. The dose-volume data from target and normal tissues will
           then be re-analyzed. From this analysis we will be better able to determine the size of
           margins needed to account for organ motion and changes such as varying amounts of gas in
           the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have
           been published.

        -  If the initial part of this trial is feasible, we will proceed to a phase I dose
           escalation trial of radiation to the at-risk lymph nodes. The primary statistical
           objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose
           (MTD) of external beam radiation based on evaluating acute toxicity. The study will be
           conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer
           than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will
           be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the
           MTD will be exceeded and the prior, lower dose cohort will be considered the MTD.
           Secondary objectives of this study are to relate patterns in gene and protein expression
           to response and toxicity and to evaluate the frequency of late term toxicity.

        -  Specific procedures and risks will be described in a separate consent to be obtained at
           the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic
           acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology
           Branch, NCI.

        -  Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images
           of the prostate and pelvis will be obtained and tissue will be acquired with biopsy
           locations precisely translated (co-registered) to an MR image of reference. A fiducial
           marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future
           radiation therapy to the prostate. If necessary, additional fiducial markers will be
           placed for prostate localization during treatment.
    

Detailed description: 
      BACKGROUND:

      -This study represents a progression from findings in four previous National Cancer Institute
      (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B,
      04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic
      Resonance (MR) biological images and co-register tissue in prostate cancer patients.

      OBJECTIVES:

      -The primary objective of the first portion of this study is to assess the feasibility of
      using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in
      prostate cancer. Also, if feasible, we hope optimize this technique with experience.

      ELIGIBILITY:

        -  This is a study of image guided, targeted radiation therapy in patients with high risk
           of nodal metastases from prostate cancer.

        -  Patients with prostate cancer who have more than 15% risk of lymph node (as defined by
           the Partin tables) metastasis will be eligible for this study.

      DESIGN:

        -  On the first 10 patients, we will perform approximately 5 computed tomography (CT)
           simulations throughout the course of their therapy. On each simulation, the initial
           treatment plan will be re-run. The dose-volume data from target and normal tissues will
           then be re-analyzed. From this analysis we will be better able to determine the size of
           margins needed to account for organ motion and changes such as varying amounts of gas in
           the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have
           been published.

        -  If the initial part of this trial is feasible, we will proceed to a phase I dose
           escalation trial of radiation to the at-risk lymph nodes. The primary statistical
           objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose
           (MTD) of external beam radiation based on evaluating acute toxicity. The study will be
           conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer
           than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will
           be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the
           MTD will be exceeded and the prior, lower dose cohort will be considered the MTD.
           Secondary objectives of this study are to relate patterns in gene and protein expression
           to response and toxicity and to evaluate the frequency of late term toxicity.

        -  Specific procedures and risks will be described in a separate consent to be obtained at
           the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic
           acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology
           Branch, NCI.

        -  Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images
           of the prostate and pelvis will be obtained and tissue will be acquired with biopsy
           locations precisely translated (co-registered) to an MR image of reference. A fiducial
           marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future
           radiation therapy to the prostate. If necessary, additional fiducial markers will be
           placed for prostate localization during treatment.
    

Intervention name(s): Radiation
Intervention type(s): Radiation
Intervention description(s): Radiation will be given in dose escalations from 5040 Gray (cGy) to a maximum of 5900 cGy to lymph nodes.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prostate; Radiation; Cancer; Prostate Cancer