Trial Outcomes & Findings for Phase I/II Hypofractionated Radiotherapy for Prostate Cancer (NCT NCT00214097)
NCT ID: NCT00214097
Last Updated: 2019-11-25
Results Overview
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.
COMPLETED
PHASE1/PHASE2
347 participants
90 days post radiation treatment
2019-11-25
Participant Flow
Participant milestones
| Measure |
Level 1
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
3.63 gy/fr, 16 fractions, 50 patients first 10 treated with 4 fractions per week next 40 treated with 5 fractions per week
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
4.3 gy/fr, 12 fractions, 50 patients first 10 treated with 4 fractions per week next 40 treated with 5 fractions per week
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Overall Study
STARTED
|
101
|
111
|
135
|
|
Overall Study
COMPLETED
|
101
|
111
|
135
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II Hypofractionated Radiotherapy for Prostate Cancer
Baseline characteristics by cohort
| Measure |
Level I
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level II
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level III
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Total
n=347 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
67 years
n=99 Participants
|
67 years
n=107 Participants
|
68 years
n=206 Participants
|
68 years
n=157 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=99 Participants
|
111 Participants
n=107 Participants
|
135 Participants
n=206 Participants
|
347 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
4 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
76 Participants
n=99 Participants
|
98 Participants
n=107 Participants
|
118 Participants
n=206 Participants
|
292 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
25 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
51 Participants
n=157 Participants
|
|
Race/Ethnicity, Customized
White
|
78 Participants
n=99 Participants
|
84 Participants
n=107 Participants
|
108 Participants
n=206 Participants
|
270 Participants
n=157 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
31 Participants
n=157 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
17 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
45 Participants
n=157 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=157 Participants
|
|
Region of Enrollment
United States
|
101 participants
n=99 Participants
|
111 participants
n=107 Participants
|
135 participants
n=206 Participants
|
347 participants
n=157 Participants
|
PRIMARY outcome
Timeframe: 90 days post radiation treatmentTo 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.
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Number of Participants Who Experience Grade 3 or Higher Acute Toxicities
|
1 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up
|
14 Participants
|
26 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: up to 15 years from enrollmentPatients 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
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Biochemical Progression-free Survival Based on PSA Surveillance
|
91.5 percentage of participants
Interval 88.2 to 94.8
|
92.7 percentage of participants
Interval 90.0 to 95.4
|
94.1 percentage of participants
Interval 91.9 to 96.3
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: 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.
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.
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Fox Chase Bowel Survey at Baseline and 3 Years
Baseline
|
90.0 scores on a scale
Standard Deviation 10.7
|
88.0 scores on a scale
Standard Deviation 14.6
|
86.2 scores on a scale
Standard Deviation 14.6
|
|
Fox Chase Bowel Survey at Baseline and 3 Years
Year 3
|
86.3 scores on a scale
Standard Deviation 11.1
|
87.7 scores on a scale
Standard Deviation 11.6
|
85.4 scores on a scale
Standard Deviation 14.7
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: 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.
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.
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Fox Chase Bladder Survey at Baseline and 3 Years
3 years
|
79.5 scores on a scale
Standard Deviation 13.5
|
82.5 scores on a scale
Standard Deviation 10.1
|
81.1 scores on a scale
Standard Deviation 12.2
|
|
Fox Chase Bladder Survey at Baseline and 3 Years
Baseline
|
84.2 scores on a scale
Standard Deviation 9.4
|
84.7 scores on a scale
Standard Deviation 10.1
|
82.7 scores on a scale
Standard Deviation 11.3
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: 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.
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.
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
International Index of Erectile Function (IIEF) Score at Baseline and 3 Years
Baseline
|
15.6 scores on a scale
Standard Deviation 11.7
|
17.6 scores on a scale
Standard Deviation 11.7
|
15.1 scores on a scale
Standard Deviation 11.1
|
|
International Index of Erectile Function (IIEF) Score at Baseline and 3 Years
3 years
|
10.4 scores on a scale
Standard Deviation 10.6
|
13.6 scores on a scale
Standard Deviation 11.7
|
9.6 scores on a scale
Standard Deviation 8.9
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: 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.
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.
Outcome measures
| Measure |
Level 1
n=101 Participants
2.94 gy/fr, 22 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 Participants
3.63 gy/fr, 16 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 Participants
4.3 gy/fr, 12 fractions,
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years
Baseline
|
9.7 scores on a scale
Standard Deviation 0.7
|
9.4 scores on a scale
Standard Deviation 1.2
|
9.5 scores on a scale
Standard Deviation 1.4
|
|
Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years
Year 3
|
9.5 scores on a scale
Standard Deviation 1.4
|
9.8 scores on a scale
Standard Deviation 0.4
|
9.5 scores on a scale
Standard Deviation 1.4
|
Adverse Events
Level 1
Level 2
Level 3
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Level 1
n=101 participants at risk
2.94 gy/fr, 22 fractions, minimum 50 patients to escalate, (back filling permitted while next dose level data matures for escalation) first 10 treated with 4 fractions per week next 40 + treated with 5 fractions per week
Radiotherapy: Daily radiation to prescribed dose
|
Level 2
n=111 participants at risk
3.63 gy/fr, 16 fractions, minimum 50 patients ( back filling permitted while next dose level data matures for escalation) first 10 treated with 4 fractions per week next 40 + treated with 5 fractions per week
Radiotherapy: Daily radiation to prescribed dose
|
Level 3
n=135 participants at risk
4.3 gy/fr, 12 fractions, 50 patients, for safety, up to an additional 100 for phase II component of study first 10 treated with 4 fractions per week next 40 +treated with 5 fractions per week
Radiotherapy: Daily radiation to prescribed dose
|
|---|---|---|---|
|
Gastrointestinal disorders
Acute GI
|
3.0%
3/101 • Number of events 3 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
5.4%
6/111 • Number of events 6 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
2.2%
3/135 • Number of events 3 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
|
Renal and urinary disorders
Acute GU
|
22.8%
23/101 • Number of events 23 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
21.6%
24/111 • Number of events 24 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
14.8%
20/135 • Number of events 20 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
|
Renal and urinary disorders
Late GI and GU toxicities
|
13.9%
14/101 • Number of events 14 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
23.4%
26/111 • Number of events 26 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
21.5%
29/135 • Number of events 29 • Acute GI and GU toxicities and Late GI and GU toxicities were recorded for the duration of the study. For level 1 patients, median followup was 100 months, for level 2 patients median follow up was 85.5 months and for level 3 it was 61.7 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place