Trial Outcomes & Findings for Radiation Therapy in Treating Patients With Prostate Cancer (NCT NCT01434290)

Last Updated: 2022-06-09

Results Overview

The co-primary endpoint is the percentage of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) bowel domain score from baseline to 1 year that exceeds 5 points (baseline - one year \> 5). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). 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 better health related quality of life. Arms are not compared to each other.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

255 participants

Primary outcome timeframe

Baseline and one year from the end of protocol treatment

Results posted on

2022-06-09

Participant Flow

Participant milestones

Participant milestones
Measure	5 Fractions 36.25 Gy IMRT (intensity modulated radiation therapy) in 5 fractions over two and a half weeks	12 Fractions 51.6 Gy IMRT in 12 fractions over two and a half weeks
Overall Study STARTED	127	128
Overall Study COMPLETED	119	121
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	5 Fractions 36.25 Gy IMRT (intensity modulated radiation therapy) in 5 fractions over two and a half weeks	12 Fractions 51.6 Gy IMRT in 12 fractions over two and a half weeks
Overall Study Protocol Violation	6	3
Overall Study No protocol treatment	2	4

Baseline Characteristics

Radiation Therapy in Treating Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 Fractions n=119 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks	Total n=240 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	66 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	121 Participants n=7 Participants	240 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: Eligible patients who started protocol treatment and completed the bowel domain of the EPIC at baseline and one year

Outcome measures

Outcome measures
Measure	5 Fractions n=93 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=100 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points	30.1 percentage of participants Interval 20.8 to 39.4	28.0 percentage of participants Interval 19.2 to 36.8

PRIMARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: Eligible patients who started protocol treatment and completed the urinary domain of the EPIC at baseline and one year

The co-primary endpoint is the proportion of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) urinary domain score from baseline to 1 year that exceeds 2 points (baseline - one year \> 2). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). 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 better health related quality of life. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=93 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=100 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points	45.2 percentage of participants Interval 35.4 to 55.0	42.0 percentage of participants Interval 32.3 to 51.7

SECONDARY outcome

Timeframe: Start of protocol treatment to one year from the end of protocol treatment

Population: Eligible patients who started protocol treatment

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of radiation therapy (RT). The high dose RT arm of Radiation Therapy Oncology Group (RTOG) study RTOG-0126 (NCT00033631) reported 1% of patients experienced grade 3+ GI/GU acute toxicity with no patient experiencing a grade 4 or 5 toxicity. If the lower confidence interval is \>1%, then that arm will be further investigated for acceptability. A late adverse event is defined as the first occurrence of worst severity of adverse event \>30 days after RT completion. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=119 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm Acute	1.7 percentage of participants Interval 0.2 to 5.9	1.7 percentage of participants Interval 0.2 to 5.9
Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm Late	0.8 percentage of participants Interval 0.1 to 4.2	0.8 percentage of participants Interval 0.1 to 4.2

SECONDARY outcome

Timeframe: Registration to five years

Population: Eligible patients who started protocol treatment and were at risk at the given time point

Failure occurs when the PSA is first noted to be 2 ng/mL or more than the current nadir value (PSA \> current nadir + 2) post RT completion. Time to PSA failure is defined as time from registration to the date of PSA failure, last known follow-up (censored), or death without PSA failure (competing risk). Rate of PSA failure is estimated by the cumulative incidence method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=119 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Rate of PSA Failure One year	0.0 percentage of participants Insufficient number of participants with events	0.8 percentage of participants Interval 0.1 to 4.1
Rate of PSA Failure Two years	0.0 percentage of participants Insufficient number of participants with events	0.8 percentage of participants Interval 0.1 to 4.1
Rate of PSA Failure Five years	3.4 percentage of participants Interval 1.1 to 8.0	3.5 percentage of participants Interval 1.1 to 8.0

SECONDARY outcome

Timeframe: Registration to 5 years

Population: Eligible patients who started protocol treatment and were at risk at the given time point

Disease-free survival duration is time from the date of randomization to the date of documentation of disease progression or until the date of death from any cause (censored). DFS is estimated by the Kaplan-Meier method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=119 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Rate of Disease-free Survival (DFS) One year	99.2 percentage of participants Interval 97.5 to 100.0	99.2 percentage of participants Interval 97.6 to 100.0
Rate of Disease-free Survival (DFS) Two years	99.2 percentage of participants Interval 97.5 to 100.0	97.5 percentage of participants Interval 94.7 to 100.0
Rate of Disease-free Survival (DFS) Five years	89.6 percentage of participants Interval 84.0 to 95.2	92.3 percentage of participants Interval 87.4 to 97.1

SECONDARY outcome

Timeframe: Registration to 5 years from the end of protocol treatment

Population: Eligible patients who started protocol treatment with baseline EQ-5D and at least 1 follow-up assessment (EQ-5D Index Score)

Quality-adjusted survival time combines disease-free survival time and quality of life as measured by the EuroQol 5-dimensional (EQ-5D) index score. It is calculated for each patient as the weighted sum of different time episodes and added up to total quality-adjusted life years . The EQ-5D measures health-related quality of life and consists of two parts, a general health visual analog scale and 5 general health questions. The latter questions are transformed into a single index score ranging from 0 (worst health state) to 1 (best health state). Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=90 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=85 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Mean Quality Adjusted Life Years at 5 Years	6.13 quality-adjusted life years Standard Deviation 10.55	4.87 quality-adjusted life years Standard Deviation 1.14

SECONDARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: Eligible patients who started protocol treatment and completed the respective domain of the EPIC at baseline and one year

The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). 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 better health related quality of life and a positive change from baseline indicating improvement over time. For this endpoint, in each domain, the actual change score calculated as timepoint score - baseline score will be used as the statistic.

Outcome measures

Outcome measures
Measure	5 Fractions n=93 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=100 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year 1-year Bowel	1.79 units on a scale Interval -26.79 to 53.57	0 units on a scale Interval -26.79 to 46.42
Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year 1-year Urinary	0 units on a scale Interval -25.75 to 69.42	0 units on a scale Interval -47.92 to 63.91

SECONDARY outcome

Timeframe: Baseline one year from the end of protocol treatment

Population: Eligible patients who started study treatment and completed the specified domain of the EPIC at baseline and one year

The percentage of patients with a reduction in the EPIC sexual domain score from baseline that exceeds 11 points (baseline - one year \> 11). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). 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 better health related quality of life. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=88 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=92 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points	32.9 percentage of participants Interval 23.1 to 42.7	30.4 percentage of participants Interval 21.0 to 39.8

SECONDARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: Eligible patients who started study treatment and completed the specified domain of the EPIC at baseline and one year

The percentage of patients with a reduction in the EPIC hormonal domain score from baseline that exceeds 3 points (baseline - one year \> 3). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). 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 better health related quality of life. Arms are not compared to each other.

Outcome measures

Outcome measures
Measure	5 Fractions n=90 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=97 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points	36.7 percentage of participants Interval 26.7 to 46.7	38.1 percentage of participants Interval 28.4 to 47.8

SECONDARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: All eligible patients who started study treatment and completed the EQ-5D at baseline and the specified timepoint

The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score. One, 2, and 5 years will be entered when they are available. Arms are not compared.

Outcome measures

Outcome measures
Measure	5 Fractions n=66 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=67 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Change From Baseline in EQ-5D Scores 1-year VAS	0 units on a scale Interval -30.0 to 74.0	0 units on a scale Interval -60.0 to 89.0
Change From Baseline in EQ-5D Scores 1-year Index Score	0 units on a scale Interval -0.554 to 0.2	0 units on a scale Interval -0.447 to 0.603

SECONDARY outcome

Timeframe: Baseline and one year from the end of protocol treatment

Population: Eligible patients who started study treatment and completed the questionnaire at baseline and the specified timepoint

The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The number of subjects responding "Yes" to the following questions are reported: "Do you have a penile prosthesis", "Have you used an medications or devices to aid or improve erections?". Arms are not compared to each other. One, 2, and 5 years will be entered when they are available.

Outcome measures

Outcome measures
Measure	5 Fractions n=94 Participants 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=96 Participants 51.6 Gy IMRT in 12 fractions over two and a half weeks
Utilization of Sexual Medications/Devices Questionnaire Response Frequences Baseline penile prosthesis question	6 participants	7 participants
Utilization of Sexual Medications/Devices Questionnaire Response Frequences Baseline medications/devices question	30 participants	29 participants
Utilization of Sexual Medications/Devices Questionnaire Response Frequences 1-year penile prosthesis question	2 participants	5 participants
Utilization of Sexual Medications/Devices Questionnaire Response Frequences 1-year Baseline medications/devices question	25 participants	29 participants

SECONDARY outcome

Timeframe: Study entry to 5 years from the end of protocol treatment

Population: The biomarker data will not be obtained due to lack of funding therefore no patients have outcome measure data.

Outcome measures

Outcome data not reported

Adverse Events

5 Fractions

Serious events: 1 serious events

Other events: 101 other events

Deaths: 0 deaths

12 Fractions

Serious events: 0 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	5 Fractions n=119 participants at risk 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 participants at risk 51.6 Gy IMRT in 12 fractions over two and a half weeks
Gastrointestinal disorders Anal hemorrhage	0.84% 1/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	0.00% 0/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Reproductive system and breast disorders Ejaculation disorder	0.84% 1/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	0.00% 0/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	5 Fractions n=119 participants at risk 36.25 Gy IMRT in 5 fractions over two and a half weeks	12 Fractions n=121 participants at risk 51.6 Gy IMRT in 12 fractions over two and a half weeks
Gastrointestinal disorders Constipation	8.4% 10/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	4.1% 5/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Diarrhea	23.5% 28/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	25.6% 31/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Fecal incontinence	6.7% 8/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	5.0% 6/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Gastrointestinal disorders - Other	12.6% 15/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	12.4% 15/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Hemorrhoids	7.6% 9/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	6.6% 8/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Proctitis	15.1% 18/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	17.4% 21/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Rectal hemorrhage	10.9% 13/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	4.1% 5/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Gastrointestinal disorders Rectal pain	5.0% 6/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	1.7% 2/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
General disorders Fatigue	25.2% 30/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	28.1% 34/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Psychiatric disorders Libido decreased	8.4% 10/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	5.0% 6/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Cystitis noninfective	14.3% 17/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	16.5% 20/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Hematuria	7.6% 9/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	9.1% 11/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Renal and urinary disorders - Other	27.7% 33/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	28.9% 35/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary frequency	55.5% 66/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	57.9% 70/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary incontinence	13.4% 16/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	18.2% 22/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary retention	18.5% 22/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	21.5% 26/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary tract obstruction	8.4% 10/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	5.0% 6/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary tract pain	10.9% 13/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	17.4% 21/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Renal and urinary disorders Urinary urgency	32.8% 39/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	38.8% 47/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Reproductive system and breast disorders Ejaculation disorder	9.2% 11/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	9.9% 12/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Reproductive system and breast disorders Erectile dysfunction	42.9% 51/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	36.4% 44/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.
Reproductive system and breast disorders Reproductive system and breast disorders - Other	5.0% 6/119 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.	5.0% 6/121 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.