Clinical trial NCT00124917: Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer
Official title: A Phase I Study of Image Guided Dose Escalation With Intensity Modulated Radiation Therapy (IMRT) to Histologically Confirmed Regions of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: Prostate Cancer
MRI
Fiducial Marker
IMRT
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2005-07-28
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: BACKGROUND:

-This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (RO)B 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 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of External Beam Radiation
timeFrame: 12 weeks after radiation therapy (RT)
Secondary outcomes:
measure: Number of Participants With Serious and Non-serious Adverse Events
timeFrame: 53 months and 20 days
Other outcomes:
measure: Radiation Response With Genomic and Proteomic Analyses
timeFrame: completion of therapy
measure: Correlate Toxicity With Genomic and Proteomic Analyses
timeFrame: Completion of therapy
measure: Long-term Effects and Toxicity Following Selective Intra-prostatic Dose Escalation
timeFrame: completion of therapy
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Aradhana Kaushal, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michalski JM, Winter K, Purdy JA, Perez CA, Ryu JK, Parliament MB, Valicenti RK, Roach M 3rd, Sandler HM, Markoe AM, Cox JD. Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):735-42. doi: 10.1016/S0360-3016(03)01578-5.
citation: Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8.
citation: Pollack A, Hanlon A, Horwitz EM, Feigenberg S, Uzzo RG, Price RA. Radiation therapy dose escalation for prostate cancer: a rationale for IMRT. World J Urol. 2003 Sep;21(4):200-8. doi: 10.1007/s00345-003-0356-x. Epub 2003 Sep 5.