Prostate Cancer
Conditions
Brief summary
The purpose of this study is to examine the clinical feasibility of using Intensity-modulated radiation therapy (IMRT) combined with daily pretreatment prostate localization to deliver increasingly hypofractionated treatment courses. Progressively larger fraction sizes will be delivered in a phase I design based on both acute and long-term tolerances to the treatment. The dose-per-fraction escalation design utilizes schemas that maintain an isoeffective dose for late effects, while predicting that tumor control will actually improve. The delivery of fewer, larger fractions of radiation, if proven effective and safe, would result in significant cost saving and more efficient use of resources. Phase II will commence with Maximum Tolerated Dose (MTD) finding with up to 200 additional patients being enrolled during this phase of the study.
Interventions
RADIATIONRadiotherapy
Daily radiation to prescribed dose
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
dose escalation, 3 possible dose groups, with one Phase II group based on MTD. Per protocol, while waiting for safety data to mature for escalation, protocol permitted enrollment to continue on last dose that was already proven safe. Thus Arms one and two have more than 50 subjects each.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically proven adenocarcinoma of the prostate. * Stage ≤ T2b disease, as defined by 1997 American Joint Committee on Cancer (AJCC) classification * Predicted risk of lymph node involvement (by standard nomograms) of 15% or less (24), OR histologically negative pelvic nodes * Gleason score ≤ 7 * No evidence of distant metastasis * Age 18+ * Informed consent signed in accordance with institutional protocol * Pretreatment evaluations must be completed as specified in Section 7.0. * ECOG performance status 0-1 * No previous or concurrent cancers, other than localized basal cell or squamous cell skin carcinoma, unless continually disease free for at least 5 years * No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy * Gonadotropin-releasing hormone agonist (GnRH-a) use permitted (maximum of 6 months duration). Anti-androgen therapy permitted concurrently with GnRH-a. * No previous or concurrent cytotoxic chemotherapy * No radical surgery or cryosurgery for prostate cancer * The absence of any co-morbid medical condition which would constitute a contraindication for radical radiotherapy * The absence of serious concurrent illness of psychological, familial, sociological, geographical or other concomitant conditions which do not permit adequate follow-up and compliance with the study protocol. * No current use of anticoagulation therapy, other than aspirin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience Grade 3 or Higher Acute Toxicities | 90 days post radiation treatment | To evaluate acute tolerances to dose-per-fraction escalation in the treatment of prostate cancer using optimized treatment of Intensity-modulated radiation therapy (IMRT), daily rectal balloon displacement, and transabdominal ultrasound localization of the prostate. For toxicities observed within the first 10 patients at each hypofractionation level, ≥20% acute grade 3 or higher GI or genitourinary (GU) toxicity will constitute a threshold toxicity level and will dictate a decrease in frequency of treatment by one treatment per week. Maximum tolerated dose is reached if 20% of participants experience acute toxicities grade 3 or higher. |
| Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up | from 90 days post XRT through last follow-up visit (up to 3 years) | To evaluate late radiation toxicities to dose-per fraction escalation in the treatment of prostate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fox Chase Bladder Survey at Baseline and 3 Years | Baseline and 3 years | The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life. Results for the Bladder Section are reported here. |
| Biochemical Progression-free Survival Based on PSA Surveillance | up to 15 years from enrollment | Patients will be considered to be without biochemical recurrence if either the Prostate-specific antigen (PSA) is still declining or the PSA nadir has been reached and is below 1.0ng/ml |
| Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Baseline and 3 years | The SQLI is composed of five items (activity, daily living, health, support, outlook) scored utilizing a numerical scale of 0-2. Standard scoring was also used for the SQLI survey (total score range 0-10) where higher score indicate increased QoL. |
| International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | Baseline and 3 years | The IIEF is a 15-item survey where 9-items are scored 0-5 and 6-items are scored 1-5 with a total range of 6-75. The standard scoring mechanism was used for IIEF, where the QoL items corresponded to the following domains: erectile function (score range 1-30), orgasmic function (score range 1-10), sexual desire (score range 2-10), intercourse satisfaction (score range 0-15), and overall satisfaction (score range 2-10). Higher numbers indicate increased QoL. |
| Fox Chase Bowel Survey at Baseline and 3 Years | Baseline and 3 years | The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life (QoL). Results for the Bowel Section are reported here. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Level I 2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose | 101 |
| Level II 3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose | 111 |
| Level III 4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose | 135 |
| Total | 347 |
Baseline characteristics
| Characteristic | Level I | Level II | Level III | Total |
|---|---|---|---|---|
| Age, Continuous | 67 years | 67 years | 68 years | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 98 Participants | 118 Participants | 292 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants | 11 Participants | 15 Participants | 51 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 16 Participants | 10 Participants | 31 Participants |
| Race/Ethnicity, Customized Unknown | 17 Participants | 11 Participants | 17 Participants | 45 Participants |
| Race/Ethnicity, Customized White | 78 Participants | 84 Participants | 108 Participants | 270 Participants |
| Region of Enrollment United States | 101 participants | 111 participants | 135 participants | 347 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 101 Participants | 111 Participants | 135 Participants | 347 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 22 / 101 | 18 / 111 | 20 / 135 |
| other Total, other adverse events | 40 / 101 | 56 / 111 | 52 / 135 |
| serious Total, serious adverse events | 0 / 101 | 0 / 111 | 0 / 135 |
Outcome results
Primary
Number of Participants Who Experience Grade 3 or Higher Acute Toxicities
To evaluate acute tolerances to dose-per-fraction escalation in the treatment of prostate cancer using optimized treatment of Intensity-modulated radiation therapy (IMRT), daily rectal balloon displacement, and transabdominal ultrasound localization of the prostate. For toxicities observed within the first 10 patients at each hypofractionation level, ≥20% acute grade 3 or higher GI or genitourinary (GU) toxicity will constitute a threshold toxicity level and will dictate a decrease in frequency of treatment by one treatment per week. Maximum tolerated dose is reached if 20% of participants experience acute toxicities grade 3 or higher.
Time frame: 90 days post radiation treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Level 1 | Number of Participants Who Experience Grade 3 or Higher Acute Toxicities | 1 Participants |
| Level 2 | Number of Participants Who Experience Grade 3 or Higher Acute Toxicities | 1 Participants |
| Level 3 | Number of Participants Who Experience Grade 3 or Higher Acute Toxicities | 0 Participants |
Primary
Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up
To evaluate late radiation toxicities to dose-per fraction escalation in the treatment of prostate
Time frame: from 90 days post XRT through last follow-up visit (up to 3 years)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Level 1 | Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up | 14 Participants |
| Level 2 | Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up | 26 Participants |
| Level 3 | Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up | 29 Participants |
Secondary
Biochemical Progression-free Survival Based on PSA Surveillance
Patients will be considered to be without biochemical recurrence if either the Prostate-specific antigen (PSA) is still declining or the PSA nadir has been reached and is below 1.0ng/ml
Time frame: up to 15 years from enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Level 1 | Biochemical Progression-free Survival Based on PSA Surveillance | 91.5 percentage of participants |
| Level 2 | Biochemical Progression-free Survival Based on PSA Surveillance | 92.7 percentage of participants |
| Level 3 | Biochemical Progression-free Survival Based on PSA Surveillance | 94.1 percentage of participants |
Secondary
Fox Chase Bladder Survey at Baseline and 3 Years
The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life. Results for the Bladder Section are reported here.
Time frame: Baseline and 3 years
Population: Unavailable quality of life questionnaires at year 3. All mean scores were adjusted for missing data. The missing data for questionnaires were handled by weighted mean imputation. Cases with more than half of the total questions missing were not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Level 1 | Fox Chase Bladder Survey at Baseline and 3 Years | Baseline | 84.2 scores on a scale | Standard Deviation 9.4 |
| Level 1 | Fox Chase Bladder Survey at Baseline and 3 Years | 3 years | 79.5 scores on a scale | Standard Deviation 13.5 |
| Level 2 | Fox Chase Bladder Survey at Baseline and 3 Years | 3 years | 82.5 scores on a scale | Standard Deviation 10.1 |
| Level 2 | Fox Chase Bladder Survey at Baseline and 3 Years | Baseline | 84.7 scores on a scale | Standard Deviation 10.1 |
| Level 3 | Fox Chase Bladder Survey at Baseline and 3 Years | 3 years | 81.1 scores on a scale | Standard Deviation 12.2 |
| Level 3 | Fox Chase Bladder Survey at Baseline and 3 Years | Baseline | 82.7 scores on a scale | Standard Deviation 11.3 |
Secondary
Fox Chase Bowel Survey at Baseline and 3 Years
The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life (QoL). Results for the Bowel Section are reported here.
Time frame: Baseline and 3 years
Population: Unavailable quality of life questionnaires at year 3. All mean scores were adjusted for missing data. The missing data for questionnaires were handled by weighted mean imputation. Cases with more than half of the total questions missing were not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Level 1 | Fox Chase Bowel Survey at Baseline and 3 Years | Year 3 | 86.3 scores on a scale | Standard Deviation 11.1 |
| Level 1 | Fox Chase Bowel Survey at Baseline and 3 Years | Baseline | 90.0 scores on a scale | Standard Deviation 10.7 |
| Level 2 | Fox Chase Bowel Survey at Baseline and 3 Years | Year 3 | 87.7 scores on a scale | Standard Deviation 11.6 |
| Level 2 | Fox Chase Bowel Survey at Baseline and 3 Years | Baseline | 88.0 scores on a scale | Standard Deviation 14.6 |
| Level 3 | Fox Chase Bowel Survey at Baseline and 3 Years | Year 3 | 85.4 scores on a scale | Standard Deviation 14.7 |
| Level 3 | Fox Chase Bowel Survey at Baseline and 3 Years | Baseline | 86.2 scores on a scale | Standard Deviation 14.6 |
Secondary
International Index of Erectile Function (IIEF) Score at Baseline and 3 Years
The IIEF is a 15-item survey where 9-items are scored 0-5 and 6-items are scored 1-5 with a total range of 6-75. The standard scoring mechanism was used for IIEF, where the QoL items corresponded to the following domains: erectile function (score range 1-30), orgasmic function (score range 1-10), sexual desire (score range 2-10), intercourse satisfaction (score range 0-15), and overall satisfaction (score range 2-10). Higher numbers indicate increased QoL.
Time frame: Baseline and 3 years
Population: Unavailable quality of life questionnaires at year 3. All mean scores were adjusted for missing data. The missing data for questionnaires were handled by weighted mean imputation. Cases with more than half of the total questions missing were not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Level 1 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | Baseline | 15.6 scores on a scale | Standard Deviation 11.7 |
| Level 1 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | 3 years | 10.4 scores on a scale | Standard Deviation 10.6 |
| Level 2 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | 3 years | 13.6 scores on a scale | Standard Deviation 11.7 |
| Level 2 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | Baseline | 17.6 scores on a scale | Standard Deviation 11.7 |
| Level 3 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | 3 years | 9.6 scores on a scale | Standard Deviation 8.9 |
| Level 3 | International Index of Erectile Function (IIEF) Score at Baseline and 3 Years | Baseline | 15.1 scores on a scale | Standard Deviation 11.1 |
Secondary
Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years
The SQLI is composed of five items (activity, daily living, health, support, outlook) scored utilizing a numerical scale of 0-2. Standard scoring was also used for the SQLI survey (total score range 0-10) where higher score indicate increased QoL.
Time frame: Baseline and 3 years
Population: Unavailable quality of life questionnaires at year 3. All mean scores were adjusted for missing data. The missing data for questionnaires were handled by weighted mean imputation. Cases with more than half of the total questions missing were not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Level 1 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Baseline | 9.7 scores on a scale | Standard Deviation 0.7 |
| Level 1 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Year 3 | 9.5 scores on a scale | Standard Deviation 1.4 |
| Level 2 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Baseline | 9.4 scores on a scale | Standard Deviation 1.2 |
| Level 2 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Year 3 | 9.8 scores on a scale | Standard Deviation 0.4 |
| Level 3 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Baseline | 9.5 scores on a scale | Standard Deviation 1.4 |
| Level 3 | Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years | Year 3 | 9.5 scores on a scale | Standard Deviation 1.4 |