Pd-103 Dose De-Escalation for Early Stage Prostate Cancer: A Prospective Randomized Trial

November 16, 2015 updated by: Gregory Merrick, M.D., Schiffler Cancer Center
The purpose of this study is to determine the most appropriate radiation implant dose for palladium-103 monotherapy. Radiation dose is related to potential cure. From previously published studies, it appears that the prescribed radiation dose can be reduced by 14-20% without any difference in potential cure (in this study, the dose is being decreased 10%). Although most patients tolerate brachytherapy well, complications to appear to be related to radiation exposure to normal structures (i.e. urethra, rectum and proximal penis). By reducing the prescribed dose, it is conceivable that fewer patients will experience side effects and complications.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In calendar year 2003, approximately 220, 000 men will be diagnosed with prostate cancer and approximately 30,000 will die. The vast majority of men will be diagnosed with clinically organ-confined disease with potentially curative treatments including radical prostatectomy, external beam radiation therapy and brachytherapy. Within the uro-oncology community, the selection of one modality over another remains controversial.

Over the past decade, transperineal ultrasound-guided permanent prostate brachytherapy using either Pd-130 or I-125 has been increasingly utilized as definitive management for early stage carcinoma of the prostate gland. This resurgence of interest in prostate brachytherapy was the result of several technologic advances including the evolution of transrectal ultrasonography, the development of a closed transperineal approach and the availability of sophisticated treatment planning computers. These imaging and planning advances significantly improved the accuracy of seed placement. In addition, the advent of CT-based postoperative dosimetry in the early 1990's provided a unique opportunity to evaluate quality and proactively predict outcome and complications.

Prostate brachytherapy represents the ultimate 3-dimensional conformal therapy and permits dose escalation far exceeding other modalities. Following permanent prostate brachytherapy with or without supplemental external beam radiation therapy, favorable long term biochemical outcomes have been reported for patients with low, intermediate and high risk features with a morbidity profile that compares favorably with competing local modalities (1,2)2).

Although there is no definitive evidence suggesting that either Pd-103 or I-125 is more efficacious than the other in terms of cure or side effects/complications, preliminary results of a prospective randomized trial suggests that Pd-103 may be more "dose forgiving" than I-125 (3). Long-term results demonstrate cancer eradication is highly correlated with delivered radiation dose. To date, postoperative dosimetry has primarily been described in terms of V 100/150/200 (volume of the gland receiving 100%, 150% and 200% of the prescription dose) and the D90 (the dose delivered to 90% of the prostate gland). Following I-125 monotherapy, A D90 greater than or equal to 140 Gy (day 30 dosimetry) is required for optimal long-term biochemical control (4,5)4)5). A dose of 140 Gy represents 96% of the standard I-125 prescription dose (145 Gy). In contrast, following Pd-103 monotherapy, A D90 greater than or equal to 100 Gy (day 30 dosimetry) and a D90 greater than or equal to 108 Gy (median day 22 dosimetry) have been reported to predict optimal biochemical outcomes (6,7)6)7). These Pd-103 doses represent 80% and 86% of the standard monotherapy prescription dose (125 Gy). In addition, a prospective randomized trial demonstrated that coverage of 90% or more of the prostate by 124 Gy of Pd-103 yields 98% change of being cancer-free three years following treatment (3).

Because of some seed placement uncertainty, however, the pre-plans are designed to deliver a higher radiation dose than necessary to most of the prostate gland (8). Additionally, there is a variable amount of edema that occurs from the implant procedure, moving seeds farther away from each other, again requiring a higher planned dose than actually needed.

Delivered radiation dose is paramount to securing long-term freedom from biochemical progression. Previously Merrick and colleagues reported that postoperative dosimetric quality for Pd-103 and I-125 in terms of V 100/150/200 and D90 were independent of prostate size, isotope selection, radiation implant dose prescription, the use of supplemental external beam radiation therapy, neoadjuvant androgen deprivation therapy and patient age (8-12)8)9)10)11)12). These results demonstrate the dosimetric reproducibility of Pd-103 across all implant scenarios. A review of the last 200 consecutive Pd-103 implants at the Schiffler Cancer Center illustrates similar dosimetric outcomes for patients implanted with 125 Gy versus 115 Gy.

Although the morbidity profile of permanent prostate brachytherapy compares favorably with competing local modalities, side effects and complications do occur. Delivered radiation dose to the urethra, rectum and proximal penis strongly correlate with brachytherapy-related morbidity (2, 13-18)13)14)15)16)17)18).

In summary, the available literature suggests that the Pd-103 doses necessary for cure care substantially less than currently prescribed, postoperative dosimetry has consistently demonstrated high intraprostatic doses and brachytherapy-related morbidity is related to radiation doses to normal surrounding structures. As such, we proposed to conduct a prospective randomized trial evaluating the effect of a 12% reduction in prescription dose (125 Gy vs. 110 Gy) on the ultimate cure and complication rates for low risk prostate cancer (PSA greater than or equal to 10 ng/mL, Gleason score greater than or equal to 6 and clinical stage T1b-T2b). To assure that the dose is adequate, intraoperative and postoperative dosimetry will be performed. Intraoperative dose evaluation will allow additional seeds to be implanted if needed to achieve minimum required dose.

Study Type

Interventional

Enrollment (Actual)

319

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98108-1597
        • Radiation Oncology 174 Department of Veterans Affairs
    • West Virginia
      • Wheeling, West Virginia, United States, 26003
        • Schiffler Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Low risk patients: Gleason score less than or equal to 6, PSA less than or equal to 10 ng/mL and clinical stage T1b-T2b (2002 AJCC.
  • An enzymatic prostatic acid phosphatase must be obtained prior to implantation.
  • No pelvic external beam radiation therapy for either prostate cancer or other malignancies.
  • Androgen deprivation therapy less than 4 month duration for size reduction is allowable.
  • No surgical staging for prostate cancer.
  • A minimum of 5 year life expectancy.
  • No other invasive cancer diagnosis other than non-melanoma skin cancer within the last 5 years.

Exclusion Criteria:

  • Exclusion criteria will be limited to patients who do not meet the above eligibility criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 125Gy prescription dose Pd-103
Radiation: Pd-103
Active Comparator: 110 Gy prescription dose Pd-103
Radiation: Pd-103

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA determinations will be obtained 3 months following implantation and then every 6 months.
Time Frame: every 6 months after inital PSA done at 3 months.
PSA determinations will be obtained 3 months following implantation and then every 6 months.
every 6 months after inital PSA done at 3 months.
Androgen deprivation therapy will not be initiated unless the PSA exceeds 10 ng/mL or distant metastases are detected.
Time Frame: depends on outcome
Androgen deprivation therapy will not be initiated unless the PSA exceeds 10 ng/mL or distant metastases are detected.
depends on outcome

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Following brachytherapy, I-PSS will be obtained on months 1, 3, 6, 12, 18, 24, 36, 48, 60.
Time Frame: months 1, 3, 6, 12, 18, 24, 36, 48, 60.
Following brachytherapy, I-PSS will be obtained on months 1, 3, 6, 12, 18, 24, 36, 48, 60.
months 1, 3, 6, 12, 18, 24, 36, 48, 60.
Following brachytherapy, R-FAS will be obtained on months 12, 36 and 60.
Time Frame: months 12, 36 and 60.
Following brachytherapy, R-FAS will be obtained on months 12, 36 and 60.
months 12, 36 and 60.
Following brachytherapy, IIEF will be obtained on months 12, 36 and 60.
Time Frame: months 12, 36 and 60.
Following brachytherapy, IIEF will be obtained on months 12, 36 and 60.
months 12, 36 and 60.
Post implant quality of life evaluations will be forwarded to Dr. G. Merrick as appropriate.
Time Frame: as needed
Post implant quality of life evaluations will be forwarded to Dr. G. Merrick as appropriate.
as needed

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Schiffler Cancer Center

Investigators

  • Principal Investigator: Gregory S. Merrick, MD, Schiffler Cancer Center, Wheeling, WV
  • Study Chair: Kent E. Wallner, MD, Department of Veterans Affairs, Seattle, WA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

October 28, 2005

First Submitted That Met QC Criteria

October 28, 2005

First Posted (Estimate)

November 1, 2005

Study Record Updates

Last Update Posted (Estimate)

November 17, 2015

Last Update Submitted That Met QC Criteria

November 16, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-8-3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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