Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer

BACKGROUND:

-This study represents a progression from findings in four previous NCI 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 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 MRI and MR biological images, such as 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 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 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 cGy.)

- The trial will accrue 18 to 36 patients with an anticipated accrual period of 2 years.

- INCLUSION CRITERIA:

1. 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 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

- PT/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 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 PI or associates to make the patient ineligible
for protocol investigations, procedures, and high-dose external beam radiotherapy.