Internal Radiation Therapy With or Without External-Beam Radiation Therapy in Treating Patients With Localized Prostate Cancer

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00714753
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 64
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying the side effects of internal radiation therapy when given with or without external-beam radiation therapy and to see how well it works in treating patients with localized prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: brachytherapy; Radiation: hypofractionated radiation therapy; Radiation: image-guided radiation therapy; Radiation: intensity-modulated radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Evaluate the tolerability of 2 radiotherapeutic regimens (high dose-rate brachytherapy [HDR] with or without image-guided intensity-modulated hypofractionated external beam radiotherapy [EBRT]), as measured by the Common Terminology Criteria for Adverse Events (CTCAE v3.0), in patients with localized prostate cancer.

Secondary

• Identify any associations between dose-volume parameters for organs at risk and the rate and severity of genitourinary or gastrointestinal adverse events.

• Evaluate patient preference with regard to selection of a second treatment (a second HDR brachytherapy session or an EBRT session).

• Evaluate patient-reported health-related quality of life (HRQOL) as measured by validated HRQOL instruments for 5 years.

• Describe the probability of freedom from biochemical and clinical failure.

• Describe the probability of freedom from salvage androgen suppression.

OUTLINE: Patients undergo high dose-rate (HDR) brachytherapy (2 fractions ≥ 5 hours apart). Beginning 2-4 weeks after completion of the first HDR brachytherapy session, patients undergo either a second session of HDR brachytherapy (2 fractions ≥ 5 hours apart) OR image-guided intensity-modulated hypofractionated external beam radiotherapy once daily 5 days a week for 3 weeks.

Quality of life is assessed at baseline, prior to the second treatment session, at 1 and 6 months after completion of treatment, every 6 months for 3 years, and then annually for 2 years.

After completion of study treatment, patients are followed at 1 and 6 months, every 6 months for 3 years, and then annually for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Evaluation of High Dose-Rate Brachytherapy ± Image-Guided Intensity Modulated Hypofractionated External Radiotherapy for Localized Prostate Cancer
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention Group Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.

Radiation: brachytherapy; Radiation: hypofractionated radiation therapy; Radiation: image-guided radiation therapy; Radiation: intensity-modulated radiation therapy

Outcome Measures

Primary Outcome Measures

1. Treatment Tolerance (Genitourinary [GU] or Gastrointestinal [GI] Adverse Events) [From baseline to 3 years after registration]

   Separately evaluate the tolerance of 2 radiotherapeutic regimens (HDR alone and HDR followed by hypofractionated EBRT) using the Common Terminology Criteria for Adverse Events (CTCAE v3.0). The specific adverse events (AEs) are early (i.e., within 270 days of treatment completion) grade >3 genitourinary (GU) and/or gastrointestinal (GI) AEs, late grade 2 GU and GI AEs, and late grade ≥3 GU and GI AEs.

Secondary Outcome Measures

1. Association Between Dose-volume Limitations for Organs at Risk and Rate and Severity of GU or GI Adverse Events [From baseline to 5 years after registration]

   Dose-volume limitations for organs at risk will be analyzed byassociating GU or GI AEs (both rate and severity) with dosimetric parameters using simple correlational methods. These parameters will include (1) bladder V80, V60, V50, and Dmax; (2) penile bulb median dose; (3) rectum V80, V60, V50 and Dmax; and (4) urethra V120, V110, V100, and Dmax.

2. Patient Preference for a Second Treatment (a Second High Dose-rate Brachytherapy Session or an External Beam Radiotherapy Session) [From baseline until the end of the first treatment]

   Patient preference for second treatment (group 1 or group 2) will be assessed using a Treatment Preference Questionnaire (Appendix IX) developed specifically for this study. Qualitative and quantitative analyses will be performed on patient responses to the questions posed after choosing their second treatment in an exploratory fashion.

3. Changes in Health-related Quality of Life Scores [From baseline to 5 years after registration]

   A pretest-posttest design will be employed to detect changes in HRQOL scores over time. The HRQOL scores will be calculated per assessment, as appropriate. Each construct will be standardized to a range of 0-100 so that comparison across constructs is facilitated. Sets of difference scores will be computed: 1) differences between baseline and treatment completion (at 1 month post treatment follow up), and 2) differences between treatment completion and all post-treatment follow-up examinations for up to five years after finishing the protocol treatment (see Section 4.1 for specific HRQOL instruments to be completed at follow-up visits). The first analysis will allow for determination of the short-term impact of treatment on HRQOL, while the second will investigate the long-term treatment effect. Student's t-test methodology will be applied to the differences at end of treatment (1 month post treatment follow up) and at each follow-up.

4. Freedom From Biochemical and Clinical Failure [From baseline to 5 years after registration]

   Freedom from biochemical and clinical failure, will be analyzed using Kaplan-Meier procedures. Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from biochemical and clinical failure.

5. Freedom From Salvage Androgen Suppression Treatment [From baseline to 5 years after registration]

   Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from salvage androgen suppression therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate, meeting one of the following criteria:

• Low-risk disease (T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/mL)

• Low intermediate-risk disease (T1-T2c, Gleason score ≤ 6, and PSA < 20 ng/mL OR T1-T2a, Gleason score 7, and PSA < 10 ng/mL)

• No known nodal (N0 or NX) or distant (M0 or MX) metastases

• No pubic arch interference, as defined by either of the following:

• Maximum transrectal ultrasound-determined anterior-posterior (z-axis) dimension < 4.3 cm

• No more than 25% prostate volume blocked (by pubic arch) on CT scan simulation at A10°I beam's eye view

• Prostate planimetry volume ≤ 60 cc as determined by step-section transrectal ultrasound

• American Urological Association voiding symptom index ≤ 12

• Peak uroflow rate (Q_max) ≥ 12 cc/second

• Post-void ultrasound bladder residual volume ≤ 100 cc

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• Life expectancy ≥ 5 years

• WBC > 2,000/μL

• Platelet count > 100,000/μL

• PT < 1.5 times upper limit of normal

• No diabetes mellitus associated with vascular ulcers or wound-healing problems

• No blood dyscrasias

• No inflammatory bowel disease

• No connective tissue disorder

• No other prior or concurrent invasive malignancy (except nonmelanoma skin cancer) or lymphomatous or hematological malignancy (except chronic lymphocytic leukemia/lymphoma) unless patient has been continually disease-free for ≥ 5 years

• No medical or psychiatric condition that would preclude giving informed consent or complying with study treatment

• Able to undergo anesthesia

PRIOR CONCURRENT THERAPY:

• No prior transurethral resection of the prostate

• No prior prostatic cryoablation or high-intensity focused ultrasound

• No prior prostatectomy

• No prior prostatic enucleation

• No prior pelvic external beam radiotherapy

• No prior radionuclide prostate brachytherapy

• No prior hemi- or total hip arthroplasty

• Neoadjuvant androgen suppression therapy allowed provided it was initiated 2-6 months prior to study entry and its total duration is ≤ 6 months

• No concurrent anticoagulation therapy, including heparin or coumadin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Thomas M. Pisansky, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00714753
• Other Study ID Numbers: CDR0000600446; P30CA015083; MC0652; 08-001451
• First Posted: Jul 14, 2008
• Last Update Posted: Aug 7, 2019
• Last Verified: Aug 1, 2018

• Keywords provided by Mayo Clinic: stage I prostate cancer; stage II prostate cancer; adenocarcinoma of the prostate
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Period Title: Overall Study
STARTED	5
HDR Brachytherapy	5
External Beam Radiotherapy (EBRT)	1
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Overall Participants	5
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	69.0
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%

Outcome Measures

1. Primary Outcome

Title	Treatment Tolerance (Genitourinary [GU] or Gastrointestinal [GI] Adverse Events)
Description	Separately evaluate the tolerance of 2 radiotherapeutic regimens (HDR alone and HDR followed by hypofractionated EBRT) using the Common Terminology Criteria for Adverse Events (CTCAE v3.0). The specific adverse events (AEs) are early (i.e., within 270 days of treatment completion) grade >3 genitourinary (GU) and/or gastrointestinal (GI) AEs, late grade 2 GU and GI AEs, and late grade ≥3 GU and GI AEs.
Time Frame	From baseline to 3 years after registration

Outcome Measure Data

Analysis Population Description

All patients registered to a dose escalation Phase I group were analyzed for this endpoint. Only 1 patient was registered to the HDR+EBRT arm. Due to protected health information, listing only 1 patient's results is contraindicated.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	5
Number [events]	3

2. Secondary Outcome

Title	Association Between Dose-volume Limitations for Organs at Risk and Rate and Severity of GU or GI Adverse Events
Description	Dose-volume limitations for organs at risk will be analyzed byassociating GU or GI AEs (both rate and severity) with dosimetric parameters using simple correlational methods. These parameters will include (1) bladder V80, V60, V50, and Dmax; (2) penile bulb median dose; (3) rectum V80, V60, V50 and Dmax; and (4) urethra V120, V110, V100, and Dmax.
Time Frame	From baseline to 5 years after registration

Outcome Measure Data

Analysis Population Description

No patients registered to a dose escalation Phase I group were analyzed for this endpoint. With only 5 patients, the study team deemed that the information would be unsuitable.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	0

3. Secondary Outcome

Title	Patient Preference for a Second Treatment (a Second High Dose-rate Brachytherapy Session or an External Beam Radiotherapy Session)
Description	Patient preference for second treatment (group 1 or group 2) will be assessed using a Treatment Preference Questionnaire (Appendix IX) developed specifically for this study. Qualitative and quantitative analyses will be performed on patient responses to the questions posed after choosing their second treatment in an exploratory fashion.
Time Frame	From baseline until the end of the first treatment

Outcome Measure Data

Analysis Population Description

None of the enrolled patients were analyzed for this endpoint due to too few patients.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	0

4. Secondary Outcome

Title	Changes in Health-related Quality of Life Scores
Description	A pretest-posttest design will be employed to detect changes in HRQOL scores over time. The HRQOL scores will be calculated per assessment, as appropriate. Each construct will be standardized to a range of 0-100 so that comparison across constructs is facilitated. Sets of difference scores will be computed: 1) differences between baseline and treatment completion (at 1 month post treatment follow up), and 2) differences between treatment completion and all post-treatment follow-up examinations for up to five years after finishing the protocol treatment (see Section 4.1 for specific HRQOL instruments to be completed at follow-up visits). The first analysis will allow for determination of the short-term impact of treatment on HRQOL, while the second will investigate the long-term treatment effect. Student's t-test methodology will be applied to the differences at end of treatment (1 month post treatment follow up) and at each follow-up.
Time Frame	From baseline to 5 years after registration

Outcome Measure Data

Analysis Population Description

None of the enrolled patients were analyzed for this endpoint due to too few patients.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	0

5. Secondary Outcome

Title	Freedom From Biochemical and Clinical Failure
Description	Freedom from biochemical and clinical failure, will be analyzed using Kaplan-Meier procedures. Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from biochemical and clinical failure.
Time Frame	From baseline to 5 years after registration

Outcome Measure Data

Analysis Population Description

With only 5 patients, the study team deemed that the information would be unsuitable.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	0

6. Secondary Outcome

Title	Freedom From Salvage Androgen Suppression Treatment
Description	Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from salvage androgen suppression therapy.
Time Frame	From baseline to 5 years after registration

Outcome Measure Data

Analysis Population Description

With only 5 patients, the study team deemed that this information would be unsuitable.

Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
Measure Participants	0

Adverse Events

Time Frame	Adverse events were assessed within 7 days of High Dose-Rate Radiation (HDR) and External beam radiation therapy (EBRT), and at one month after completion of therapy, 6 months after registration, then every 6 months x 5 (through year 3), then every 12 months for years 4-5, then off study. Up to 5 years.
Adverse Event Reporting Description	CTCAE term & grade: The descriptions & grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation & scientific analysis & is a single MedDRA Lowest Level Term (LLT). Only 1 patient was registered to the HDR+EBRT arm. Due to protected health information, listing only 1 patient's results is contraindicated.
Arm/Group Title	Arm 1 (HDR ± EBRT)
Arm/Group Description	Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session.
All Cause Mortality
	Arm 1 (HDR ± EBRT)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Arm 1 (HDR ± EBRT)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1 (HDR ± EBRT)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Gastrointestinal disorders
Anal hemorrhage	1/5 (20%)	1
Diarrhea	5/5 (100%)	9
Flatulence	1/5 (20%)	1
General disorders
Fatigue	1/5 (20%)	1
Infections and infestations
Abdominal infection	1/5 (20%)	1
Bladder infection	1/5 (20%)	1
Renal and urinary disorders
Bladder hemorrhage	2/5 (40%)	2
Bladder pain	1/5 (20%)	1
Bladder stenosis	1/5 (20%)	1
Cystitis	3/5 (60%)	3
Urethral hemorrhage	2/5 (40%)	2
Urethral pain	4/5 (80%)	6
Urinary frequency	4/5 (80%)	12
Urinary incontinence	3/5 (60%)	5
Urinary retention	3/5 (60%)	5
Urogenital disorder	1/5 (20%)	1
Reproductive system and breast disorders
Erectile dysfunction	4/5 (80%)	5
Perineal pain	1/5 (20%)	1
Prostatic hemorrhage	2/5 (40%)	2
Prostatic pain	3/5 (60%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.