Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer

A Phase I Study of Image Guided Dose Escalation With Intensity Modulated Radiation Therapy (IMRT) to Histologically Confirmed Regions of Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiation Therapy; Radiation to tumor area as per protocol

Radiation: Radiation; 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]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of External Beam Radiation	Maximum tolerated dose is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experienced a dose limiting toxicity attributed to radiation therapy.	12 weeks after radiation therapy (RT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and Non-serious Adverse Events	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTC v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	53 months and 20 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation Response With Genomic and Proteomic Analyses	Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with radiation response.	completion of therapy
Correlate Toxicity With Genomic and Proteomic Analyses	Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with toxicity.	Completion of therapy
Long-term Effects and Toxicity Following Selective Intra-prostatic Dose Escalation	Acute and late toxicity will be assessed by the Radiation Therapy Oncology Group (RTOG) Acute and Late Toxicity Genitourinary (GI)/Gastrointestinal (GU) scales.	completion of therapy

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aradhana Kaushal, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2005
• Primary Completion (Actual): March 6, 2011
• Study Completion (Actual): May 9, 2017

Study Registration Dates

• First Submitted: July 27, 2005
• First Submitted That Met QC Criteria: July 27, 2005
• First Posted (Estimate): July 28, 2005

Study Record Updates

• Last Update Posted (Actual): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: MRI; Prostate Cancer; IMRT; Fiducial Marker
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 050191; 05-C-0191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No