Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Radiation
Intervention description: Areas of pathologically confirmed malignancy will undergo dose escalation as described below. Areas of image abnormality that could not be biopsied or were without definite pathologic evidence of malignancy will be given intermediate doses. The remainder of the prostate gland will receive standard dose (as per the Radiation Therapy Oncology Group (RTOG) 9406 study) 7560 centigray (cGy) in 180 cGy daily fractions.[1]
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Prostate Cancer; MRI; Fiducial Marker; IMRT

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 scientific objective of this protocol is to determine the maximum tolerated dose (MTD)
      of external beam radiation to regions of interest within the prostate based acute toxicity.

      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.

      ELIGIBILITY:

      -Patients with prostate cancer without evidence of metastasis will be eligible for this
      study.

      DESIGN:

        -  This phase I trial will use intensity modulated radiation therapy (IMRT) to deliver
           escalating doses of external beam radiation to regions of histologically confirmed
           prostate cancer. The study will be conducted using a standard 3-6 dose-escalation with
           an initial 3 patients in each dose cohort and the potential expansion of the cohort to 6
           patients.

        -  Anatomic magnetic resonance imaging (MRI) and magnetic resonance (MR) biological images,
           such as magnetic resonance spectroscopy (MRS), will be obtained. Tissue will be acquired
           from sites of interest, with biopsy locations precisely translated (co-registered) to an
           MR image of reference. Tissue samples will be processed for complementary
           deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the
           Radiation Oncology Branch, NCI. A gold seed will be left at the biopsy site as a
           fiducial marker to direct future radiation therapy. If necessary, additional fiducial
           markers will be placed for target localization during treatment.

        -  Once MR guided biopsies are obtained and fiducial markers placed, the patient will
           undergo a standard computed tomography (CT) simulation for radiation therapy treatment
           planning. The MR and CT images will be fused. Areas of pathologically confirmed
           malignancy will undergo dose escalation as described below. Areas of image abnormality
           that could not be biopsied or were without definite pathologic evidence of malignancy
           will be given intermediate doses. The remainder of the prostate gland will receive
           standard dose (7560 centigray (cGy)').

        -  The trial will accrue 18 to 36 patients with an anticipated accrual period of 2 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

               2. Pathology report confirming adenocarcinoma of the prostate

               3. Risk of lymph node metastasis less than 10% as defined by the Partin tables

               4. Tumor visible on magnetic resonance imaging (MRI)

               5. No prior surgery, radiation, or chemotherapy for prostate cancer.

               6. Age greater than 18 y/o and less than 90 years old.

        EXCLUSION CRITERIA:

          1. Cognitively impaired patients who cannot give informed consent.

          2. Patients with metastatic disease.

          3. Contraindication to biopsy

               -  Bleeding disorder

               -  Prothrombin time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to
                  1.5 times the upper limit of normal

               -  Platelets less than or equal to 50K

               -  Artificial heart valve

          4. Contraindication to magnetic resonance imaging (MRI)

               -  Patients weighing greater than 136 kgs (weight limit for the scanner tables)

               -  Allergy to MR contrast agent

               -  Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable
                  electronic devices.

          5. Pre-existing and active prostatitis or proctitis

          6. Other medical conditions deemed by the principal investigator (PI) or associates to
             make the patient ineligible for protocol investigations, procedures, and high-dose
             external beam radiotherapy.