Stage III Prostate Adenocarcinoma AJCC v7, Stage II Prostate Adenocarcinoma AJCC v7, Stage I Prostate Adenocarcinoma American Joint Committee on Cancer (AJCC) v7
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. To assess feasibility of pre-operative stereotactic body radiotherapy (SBRT) in prostate cancer patients at high risk for recurrence after prostatectomy. SECONDARY OBJECTIVES: I. 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). II. Investigation of the radiobiology of SBRT in prostate cancer using resected prostate tumor tissue. III. 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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
RADIATIONStereotactic Body Radiation Therapy
Undergo SBRT
Sponsors
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Completed the Maximum Time Allowed on Study Without Severe Acute Surgical Complications | At 4 weeks post surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
The study was open to recruitment from 6/15/2016 and closed to enrollment 09/08/2019
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Body Radiation Therapy (SBRT) Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Stereotactic Body Radiation Therapy (SBRT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| CStage cT1cN1Mo | 1 Participants |
| CStage cT1cNoMo | 2 Participants |
| CStage cT2aNoMo | 2 Participants |
| CStage cT2bNoMo | 2 Participants |
| CStage cT2cN1Mo | 1 Participants |
| CStage cT3aN1Mo | 2 Participants |
| CStage cT3aNoMo | 1 Participants |
| Gleason Grade Gleason 7 | 3 Participants |
| Gleason Grade Gleason 8 | 5 Participants |
| Gleason Grade Gleason 9 | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Number of Participants Who Completed the Maximum Time Allowed on Study Without Severe Acute Surgical Complications
Time frame: At 4 weeks post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants Who Completed the Maximum Time Allowed on Study Without Severe Acute Surgical Complications | 11 Participants |
Secondary
Changes in Quality of Life as Measured on the International Prostate Symptom Score (IPSS) Questionnaire.
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.
Population: Three patients dd not complete the QOL assessment and therefore were not included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life as Measured on the International Prostate Symptom Score (IPSS) Questionnaire. | 0.5 change in score on a scale |
Secondary
Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring.
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. | Urinary Incontinence | -32.8 score on a scale |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. | urinary irritative/obstructive | -1.6 score on a scale |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. | Bowel | -2.1 score on a scale |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. | Sexual Function | -34.4 score on a scale |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Changes in Quality of Life (QOL) ,From Baseline to 12 Months, as Measured on the Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Scoring. | Hormonal | -10.6 score on a scale |
Secondary
Correlative Biomarker Analyses Using Tissue and Serial Blood Samples
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
Population: Pre-treatment biopsies and surgical specimens from this trial were used to determine radiation-induced changes in macrophage subsets. Six participants had available paired biopsy cores and Radical Prostatectomy (RP) specimens for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD11b | 0.002 Macropahge cells per pixel area | Standard Deviation 0.07 |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD68 | 0.01 Macropahge cells per pixel area | Standard Deviation 0.05 |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD163 | 0.005 Macropahge cells per pixel area | Standard Deviation 0.05 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD11b | 0.004 Macropahge cells per pixel area | Standard Deviation 0.01 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD68 | 0.035 Macropahge cells per pixel area | Standard Deviation 0.01 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD163 | 0.03 Macropahge cells per pixel area | Standard Deviation 0.07 |
Secondary
Correlative Biomarker Analyses Using Tissue and Serial Blood Samples
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
Population: Pre-treatment biopsies and surgical specimens from this trial were used to determine radiation-induced changes in T cell. Six participants had available paired biopsy cores and RP specimens for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD3+CD8 | 70 cells per Tumor area mm2 | Standard Deviation 15 |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD3+CD4 | 110 cells per Tumor area mm2 | Standard Deviation 10 |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD4+FOXp3 | 30 cells per Tumor area mm2 | Standard Deviation 10 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD3+CD8 | 30 cells per Tumor area mm2 | Standard Deviation 10 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD3+CD4 | 90 cells per Tumor area mm2 | Standard Deviation 20 |
| Post SBRT and Radical Prostatectomy (RP) | Correlative Biomarker Analyses Using Tissue and Serial Blood Samples | CD4+FOXp3 | 50 cells per Tumor area mm2 | Standard Deviation 15 |
Secondary
Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities
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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Gastrointestinal toxicities | Grade 3 | 0 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Genitourinary Toxicities | Grade 0 | 1 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Genitourinary Toxicities | Grade 1 | 4 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Genitourinary Toxicities | Grade 2 | 4 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Genitourinary Toxicities | Grade 3 | 2 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Gastrointestinal toxicities | Grade 0 | 9 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Gastrointestinal toxicities | Grade 1 | 1 Participants |
| Treatment Stereotactic Body Radiotherapy (SBRT) | Number of Participants With Genitourinary Toxicities and Gastrointestinal Toxicities | Gastrointestinal toxicities | Grade 2 | 1 Participants |