Stereotactic Body Radiation Therapy in Treating Patients With High-Risk Prostate Cancer Undergoing Surgery

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02830165
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 66.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase I trial studies stereotactic body radiation therapy (SBRT) in treating patients with prostate cancer that is likely to come back or spread (high-risk) undergoing surgery. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Delivering radiotherapy before prostatectomy by SBRT is more convenient, conformal, and may spare normal tissues better than delivering radiotherapy after prostatectomy.

Condition or Disease	Intervention/Treatment	Phase
Stage I Prostate Adenocarcinoma American Joint Committee on Cancer (AJCC) v7; Stage II Prostate Adenocarcinoma AJCC v7; Stage III Prostate Adenocarcinoma AJCC v7	Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Radiation: Stereotactic Body Radiation Therapy	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To assess feasibility of pre-operative stereotactic body radiotherapy (SBRT) in prostate cancer patients at high risk for recurrence after prostatectomy.

SECONDARY OBJECTIVES:

1. To assess safety and acute toxicity of SBRT followed by prostatectomy. This will be based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and patient reported quality of life (Expanded Prostate Cancer Index Composite [EPIC] and International Prostate Symptom Score [IPSS] questionnaires).

2. Investigation of the radiobiology of SBRT in prostate cancer using resected prostate tumor tissue.

3. Evaluation of the nature of the immune response to prostate cancer generated by SBRT.

OUTLINE:

Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.

After completion of the study treatment, patients are followed up at 0 to 4 weeks, and every 3 months for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Feasibility Trial of Preoperative Adjuvant Stereotactic Body Radiotherapy for Patients at High Risk of Local Failure After Prostatectomy
• Actual Study Start Date: Jun 15, 2016
• Actual Primary Completion Date: May 9, 2020
• Anticipated Study Completion Date: Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (SBRT) Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Radiation: Stereotactic Body Radiation Therapy; Undergo SBRT; Other Names: SABR SBRT Stereotactic Ablative Body Radiation Therapy

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Completed the Maximum Time Allowed on Study Without Severe Acute Surgical Complications [At 4 weeks post surgery]

Secondary Outcome Measures

1. Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities [Up to 1 year]

   Based on the Common Terminology Criteria for Adverse Events (CTCAE) v4. Grade refers to the severity of the adverse event. Indications are Grade 1 is Mild, Grade 2 is Moderate, Grade 3 is Severe or medically significant but not immediately life threatening. Grade 0 refers to absence of an adverse event (ae).

2. Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. [score from baseline to twelve months]

   The Expanded Prostate Cancer Index Composite Short Form (EPIC-26) is composed of 26 items and measures health-related quality of life across 5 prostate cancer domains. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing a better quality of life.

3. Changes in Quality of Life as Measured on the International Prostate Symptom Score (IPSS) Questionnaire. [Mean change in I-PSS score from baseline to 12 months.]

   The International Prostate Symptom Score is composed of seven questions and scored from 0 - 35, with higher scores indicating more severe symptoms.

Other Outcome Measures

1. Correlative Biomarker Analyses Using Tissue and Serial Blood Samples [Baseline and to up to 1 year]

   Tissue specimens of the primary tumor as well as blood draws before and after treatment will be used to conduct biomarker and molecular analyses relevant to understanding the biology of prostate SBRT

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed primary non-metastatic adenocarcinoma of the prostate

• Patient desires and is medically fit to undergo prostatectomy

• Karnofsky performance status (KPS) >= 70

• Patients on androgen deprivation therapy (ADT) are allowed

• For confirmation of high risk local failure status, patients will have any one of the following:

• Computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating seminal vesicle invasion (SVI) or extraprostatic extension (EPE) within 1 year of enrollment into the study

• Pre-biopsy prostate-specific antigen (PSA) >= 20

• Gleason score 7-10 (Gleason 7 must be 4+3), presence of any Gleason 5 (even if a tertiary score) as determined at diagnostic biopsy

• Gleason score 7 and > 50% of biopsy cores positive for prostate cancer

• Clinical stage >= T3 (staging by imaging acceptable)

• An image-guided biopsy (via Artemis Ultrasound with MRI co-registration) is encouraged but not required if not performed as standard of care biopsy

Exclusion Criteria:

• Distant metastases, based upon:

• CT scan or MRI of the abdomen/pelvis or prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) within 120 days prior to registration and

• Bone scan or PSMA PET/CT within 120 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis prior to registration

• Patient is unable or unwilling to sign consent

• Patient is considered low-risk and would not have received adjuvant radiation therapy (RT) outside of this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nicholas Nickols, MD, PhD, UCLA / Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 4, 2018
• Informed Consent Form - Aug 28, 2019

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02830165
• Other Study ID Numbers: 15-001580; NCI-2016-00188; JCCCID608; P50CA092131
• First Posted: Jul 12, 2016
• Last Update Posted: Jan 6, 2022
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Adenocarcinoma; Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The study was open to recruitment from 6/15/2016 and closed to enrollment 09/08/2019

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 36.4%
>=65 years	7 63.6%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%
Gleason Grade (Count of Participants)
Gleason 9	3 27.3%
Gleason 8	5 45.5%
Gleason 7	3 27.3%
CStage (Count of Participants)
cT1cNoMo	2 18.2%
cT1cN1Mo	1 9.1%
cT2aNoMo	2 18.2%
cT2bNoMo	2 18.2%
cT2cN1Mo	1 9.1%
cT3aNoMo	1 9.1%
cT3aN1Mo	2 18.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Completed the Maximum Time Allowed on Study Without Severe Acute Surgical Complications
Time Frame	At 4 weeks post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Stereotactic Body Radiotherapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Measure Participants	11
Count of Participants [Participants]	11 100%

2. Secondary Outcome

Title	Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities
Description	Based on the Common Terminology Criteria for Adverse Events (CTCAE) v4. Grade refers to the severity of the adverse event. Indications are Grade 1 is Mild, Grade 2 is Moderate, Grade 3 is Severe or medically significant but not immediately life threatening. Grade 0 refers to absence of an adverse event (ae).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Measure Participants	11
Grade 0	1 9.1%
Grade 1	4 36.4%
Grade 2	4 36.4%
Grade 3	2 18.2%
Grade 0	9 81.8%
Grade 1	1 9.1%
Grade 2	1 9.1%
Grade 3	0 0%

3. Secondary Outcome

Title	Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring.
Description	The Expanded Prostate Cancer Index Composite Short Form (EPIC-26) is composed of 26 items and measures health-related quality of life across 5 prostate cancer domains. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing a better quality of life.
Time Frame	score from baseline to twelve months

Outcome Measure Data

Analysis Population Description

Mean change in EPIC-26 score from baseline to 12 months. Three patients dd not complete the QOL assessment and therefore were not included in the analysis.

Arm/Group Title	Treatment Stereotactic Body Radiotherapy (SBRT)
Arm/Group Description	Change in score from baseline at 12 months. Quality-of-Life Assessment: Ancillary studies
Measure Participants	8
Urinary Incontinence	-32.8
urinary irritative/obstructive	-1.6
Bowel	-2.1
Sexual Function	-34.4
Hormonal	-10.6

4. Secondary Outcome

Title	Changes in Quality of Life as Measured on the International Prostate Symptom Score (IPSS) Questionnaire.
Description	The International Prostate Symptom Score is composed of seven questions and scored from 0 - 35, with higher scores indicating more severe symptoms.
Time Frame	Mean change in I-PSS score from baseline to 12 months.

Outcome Measure Data

Analysis Population Description

Three patients dd not complete the QOL assessment and therefore were not included in the analysis.

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Measure Participants	8
Mean (95% Confidence Interval) [change in score on a scale]	0.5

5. Other Pre-specified Outcome

Title	Correlative Biomarker Analyses Using Tissue and Serial Blood Samples
Description	Tissue specimens of the primary tumor as well as blood draws before and after treatment will be used to conduct biomarker and molecular analyses relevant to understanding the biology of prostate SBRT
Time Frame	Baseline and to up to 1 year

Outcome Measure Data

Analysis Population Description

Exploratory outcome measure analysis are in process and ongoing

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
Measure Participants	0

Adverse Events

Time Frame	90 day intervals for 1 year
Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.
All Cause Mortality
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)
Renal and urinary disorders
Urinary Tract Infection	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Eye disorders
Bilateral Eye Irritation and Redness	1/11 (9.1%)	1
Gastrointestinal disorders
Diarrhea	2/11 (18.2%)	2
Hemorrhoids	2/11 (18.2%)	2
Increased Bowel Movement	1/11 (9.1%)	1
Loose Bowel Movement	1/11 (9.1%)	1
Loose Stools	1/11 (9.1%)	1
General disorders
Erectile Dysfunction	4/11 (36.4%)	4
Loss of Sexual Function	1/11 (9.1%)	1
Mild Pain	1/11 (9.1%)	1
Painless Hematuria	1/11 (9.1%)	1
Radiation Colopathy and Proctopathy	1/11 (9.1%)	1
Rectal Bleeding	1/11 (9.1%)	1
Slight Burning when Urinating	1/11 (9.1%)	1
Abdominal Pain	1/11 (9.1%)	1
Anxiety	2/11 (18.2%)	2
Atrial Fibrillation	1/11 (9.1%)	1
Benign Polyp	1/11 (9.1%)	1
Chills	2/11 (18.2%)	2
Dyspenea	1/11 (9.1%)	1
Edema Suprepubic	1/11 (9.1%)	1
Fatigue	5/11 (45.5%)	5
Hot Flashes	1/11 (9.1%)	1
Middle Mediastinal Schwannoma	1/11 (9.1%)	1
Nausea	1/11 (9.1%)	1
Pain	1/11 (9.1%)	1
Perineal Numbness	1/11 (9.1%)	1
Sweating	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Knee Pain	1/11 (9.1%)	1
Lower Back Pain	1/11 (9.1%)	1
Muscle Aches (neck and shoulders)	1/11 (9.1%)	1
Pseudogout	1/11 (9.1%)	1
Renal and urinary disorders
Difficulty Urinating	1/11 (9.1%)	1
Dysuria	1/11 (9.1%)	1
Incontinence	1/11 (9.1%)	1
Nocturia	3/11 (27.3%)	3
Urinary frequency	7/11 (63.6%)	7
Urinary Incontinence	6/11 (54.5%)	8
Urinary Tract Pain	1/11 (9.1%)	1
Urinary Urgency	3/11 (27.3%)	3
Urinary Tract Infection	2/11 (18.2%)	2

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.