Trial Outcomes & Findings for Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy (NCT NCT03253744)

Last Updated: 2025-10-08

Results Overview

The MTD of image-guided, focally dose escalated prostate stereotactic body radiation therapy (SBRT) in participants with a local recurrence of prostate cancer after prior radiotherapy. The MTD is the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during treatment and up to 3 weeks following completion of treatment, and the dose below that at which at least 2 (of .6) participants have DLT as a result of treatment. A DLT is a Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days, other Grade 3 in-field toxicities attributable to Stereotactic body radiation therapy (SBRT) that do not resolve to a Grade 2 or less within 4 days, and delays of more than one week in completing radiation treatment due to toxicity.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

3 weeks post-treatment

Results posted on

2025-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1, Level 1, Arm 1: 40 Gray (Gy) Tumor Irradiation Prostate and Tumor Arm 1: Tumor irradiation. Cohort 1, Level 1, Arm 1 - 40 gray (Gy) to Tumor planning target volume (PTV) External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 1, Level 2, Arm 1 - 42.5 Gray (Gy) Tumor Irradiation Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV); External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
SBRT Treatment STARTED	6	2	3	6
SBRT Treatment COMPLETED	6	2	3	6
SBRT Treatment NOT COMPLETED	0	0	0	0
Completed Dose-Limiting Toxicity Assess. STARTED	6	2	3	6
Completed Dose-Limiting Toxicity Assess. COMPLETED	6	2	3	6
Completed Dose-Limiting Toxicity Assess. NOT COMPLETED	0	0	0	0
Completion of Follow-Up STARTED	6	2	3	6
Completion of Follow-Up COMPLETED	4	2	3	2
Completion of Follow-Up NOT COMPLETED	2	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1, Level 1, Arm 1: 40 Gray (Gy) Tumor Irradiation Prostate and Tumor Arm 1: Tumor irradiation. Cohort 1, Level 1, Arm 1 - 40 gray (Gy) to Tumor planning target volume (PTV) External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 1, Level 2, Arm 1 - 42.5 Gray (Gy) Tumor Irradiation Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV); External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Completion of Follow-Up Continuing follow-up.	2	0	0	4

Baseline Characteristics

Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1, Level 1, Arm 1: 40 Gray (Gy) Tumor Irradiation Prostate and Tumor n=6 Participants Arm 1: Tumor irradiation. Cohort 1, Level 1, Arm 1 - 40 gray (Gy) to Tumor planning target volume (PTV) External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 1, Level 2, Arm 1 - 42.5 Gray (Gy) Tumor Irradiation n=2 Participants Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV); External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation n=3 Participants Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation n=6 Participants Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	14 Participants n=21 Participants
Age, Continuous	71.02 years STANDARD_DEVIATION 5.65 • n=5 Participants	78.3 years STANDARD_DEVIATION 5.66 • n=7 Participants	72.7 years STANDARD_DEVIATION 4.17 • n=5 Participants	65.95 years STANDARD_DEVIATION 4.51 • n=4 Participants	70.38 years STANDARD_DEVIATION 6.07 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	17 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	17 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants	17 participants n=21 Participants

PRIMARY outcome

Timeframe: 3 weeks post-treatment

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Maximum Tolerated Dose (MTD)	40 gray (Gy)	42.5 gray (Gy)	—	—

SECONDARY outcome

Timeframe: 6 months after radiation

The sensitivity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard to evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. Sensitivity is the number of true positives divided by the sum of the number of true positives and false negatives. Lesions detected on DCF-PyL that are biopsy confirmed are considered true positives. Lesions that are not detected on DCFPyL and are biopsy positive are considered false negatives.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Sensitivity of 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid (18F-DCFPyL) Imaging as Compared to Biopsy in Detecting Locally Recurrent Prostate Cancer	95 Percent Interval 82.0 to 99.0	100 Percent Interval 88.0 to 100.0	—	—

SECONDARY outcome

Timeframe: 6 months after radiation

The specificity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard to evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. Specificity is the number of true negatives divided by the sum of the number of true negatives and the number of false positives. Lesions that are not detected on DCF-PyL that are biopsy confirmed to have no tumor are considered true negatives. Lesions that are detected on DCF-PyL and are biopsy negative are considered false positives.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Specificity of 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid (18F-DCFPyL) Imaging as Compared to Biopsy in Detecting Locally Recurrent Prostate Cancer	100 Percent Interval 96.0 to 100.0	100 Percent Interval 96.0 to 100.0	—	—

SECONDARY outcome

Timeframe: Baseline compared to 24 months after treatment

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes (Sexual Health Inventory for Men (SHIM), in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The SHIM is a 5-question quiz used to identify erectile dysfunction and assess its severity. The composite score is generated by adding the score for each question. The total score can range from 1-25. Higer values represent better erectile function.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Changes of Sexual Health Inventory for Men (SHIM) Quality of Life (QOL) Scores During and After Treatment Baseline	7.25 Scores on a scale Standard Deviation 8.36	14.33 Scores on a scale Standard Deviation 10.44	—	—
Changes of Sexual Health Inventory for Men (SHIM) Quality of Life (QOL) Scores During and After Treatment After treatment	5.75 Scores on a scale Standard Deviation 7.61	6.71 Scores on a scale Standard Deviation 9.10	—	—

SECONDARY outcome

Timeframe: Baseline compared to 24 months after treatment

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes, American Urologic Association (AUA) Symptom Index, in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The AUA Symptom Index is a 7-question quiz used to identify urinary symptoms and assess severity. Each question is scored based on the frequency of a different urinary symptoms. The composite score is generated by adding the score for each question. The total score can range from 0-35. Lower values represent less symptoms.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=3 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=6 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Changes of American Urologic Association (AUA) Symptom Index Quality of Life (QOL) Scores During and After Treatment Baseline	5.75 Scores on a scale Standard Deviation 5.48	8.77 Scores on a scale Standard Deviation 6.53	—	—
Changes of American Urologic Association (AUA) Symptom Index Quality of Life (QOL) Scores During and After Treatment After treatment	11.86 Scores on a scale Standard Deviation 9.56	8.14 Scores on a scale Standard Deviation 3.98	—	—

SECONDARY outcome

Timeframe: Baseline compared to 24 months after treatment

Changes of QOL scores during and after treatment on participant reported outcomes, EPIC-26 in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model QOL scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The EPIC-26 is a shortened, validated questionnaire used to assess health related QOL in individuals with prostate cancer. The EPIC-26 measures sexual function, bowel function, hormone therapy side effects, urinary incontinence, and urinary irritative symptoms. The survey has 26 individual items that have 4 to 5 response options that reflect a range of function from poor to excellent. The EPIC-26 uses a Likert scale for each item, and scores are transformed to a 0-100 scale, with higher scores indicating better Health-Related Quality of Life.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Changes of Expanded Prostate Cancer Index Composite (EPIC-26) Quality of Life (QOL) Scores During and After Treatment Baseline	93.75 Scores on a scale Standard Deviation 11.57	75.00 Scores on a scale Standard Deviation 25.00	—	—
Changes of Expanded Prostate Cancer Index Composite (EPIC-26) Quality of Life (QOL) Scores During and After Treatment After treatment	82.14 Scores on a scale Standard Deviation 27.82	71.43 Scores on a scale Standard Deviation 22.49	—	—

SECONDARY outcome

Timeframe: 1 and 2 years after treatment

bPFS, prostate-specific antigen (PSA) \< 2 ng/dL above post stereotactic body radiation therapy (SBRT) nadir) at 1 and 2 years after treatment with focally dose escalated SBRT for locally recurrent prostate cancer after irradiation: bPFS will be estimated by the Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model. bPFS is defined as the duration of time from start of treatment to time of PSA progression or death, whichever occurs first. PSA progression (also known as biochemical failure) is defined based on elevation of PSA 2 ng/dL beyond the post-treatment nadir PSA, using the Phoenix criteria.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Biochemical Progression Free Survival (bPFS) 1 year after treatment	100 percentage of participants	100 percentage of participants	—	—
Biochemical Progression Free Survival (bPFS) 2 years after treatment	87.5 percentage of participants	100 percentage of participants	—	—

SECONDARY outcome

Timeframe: 3 weeks after end of treatment

DLT's of image-guided, focally dose escalated prostate Stereotactic body radiation therapy (SBRT) in participants previously treated with radiotherapy. A DLT (during treatment and within the first three weeks after treatment) is defined as a Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days with appropriate medical management. Other grade 3 in-field toxicities attributable to SBRT that do not resolve to Grade 2 or less within 4 days with appropriate medical management. Delays of more than one week in completing radiation treatment due to toxicity. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 2 is moderate. Grade 3 is severe. Define the dose-limiting toxicities and toxicity profile of image-guided, focally dose escalated prostate SBRT in patients previously treated with radiotherapy: DLTs will be reported descriptively.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=8 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=9 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Dose Limiting Toxicities (DLT) Grade 3 Cystitis non-infective	1 toxicities	0 toxicities	—	—
Dose Limiting Toxicities (DLT) Grade 3 Urinary incontinence	1 toxicities	0 toxicities	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 38 months (mos) & 26 days (d) for Cohort 1, Level 1, Arm 1, 29 mos & 9 d for Cohort 1, Level 2, Arm 1, 43 mos & 12 d for Cohort 2, Level 1, Arm 1, & 26 mos & 9 d for Cohort 2, Level 2, Arm 1.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	All Participants in Arm 1 n=6 Participants All participants in Arm1: 40 Gy Tumor irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	All Participants in Arm 2 n=2 Participants All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation n=3 Participants Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation n=6 Participants Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	6 Participants	2 Participants	3 Participants	6 Participants

Adverse Events

Cohort 1, Level 1, Arm 1: 40 Gray (Gy) Tumor Irradiation Prostate and Tumor

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 1, Level 2, Arm 1 - 42.5 Gray (Gy) Tumor Irradiation

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1, Level 1, Arm 1: 40 Gray (Gy) Tumor Irradiation Prostate and Tumor n=6 participants at risk Arm 1: Tumor irradiation. Cohort 1, Level 1, Arm 1 - 40 gray (Gy) to Tumor planning target volume (PTV) External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 1, Level 2, Arm 1 - 42.5 Gray (Gy) Tumor Irradiation n=2 participants at risk Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV); External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 1, Arm 2 - 30 Gray (Gy) and 40 Gy Prostate and Tumor Irradiation n=3 participants at risk Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.	Cohort 2, Level 2, Arm 2 - 30 Gray (Gy) and 42.5 Gy Prostate and Tumor Irradiation n=6 participants at risk AArm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment. All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-\[(6-18F-fluoro-pyridine-3-carbonyl)-amino\]-pentyl} -ureido)-pentanedioic acid.
Renal and urinary disorders Hematuria	0.00% 0/6 • Date treatment consent signed to date off study, approximately 38 months and 26 days for Cohort 1, Level 1, Arm 1, 29 months and 9 days for Cohort 1, Level 2, Arm 1, 43 months and 12 days for Cohort 2, Level 1, Arm 1, and 26 months and 9 days for Cohort 2, Level 2, Arm 1.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 38 months and 26 days for Cohort 1, Level 1, Arm 1, 29 months and 9 days for Cohort 1, Level 2, Arm 1, 43 months and 12 days for Cohort 2, Level 1, Arm 1, and 26 months and 9 days for Cohort 2, Level 2, Arm 1.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 38 months and 26 days for Cohort 1, Level 1, Arm 1, 29 months and 9 days for Cohort 1, Level 2, Arm 1, 43 months and 12 days for Cohort 2, Level 1, Arm 1, and 26 months and 9 days for Cohort 2, Level 2, Arm 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 38 months and 26 days for Cohort 1, Level 1, Arm 1, 29 months and 9 days for Cohort 1, Level 2, Arm 1, 43 months and 12 days for Cohort 2, Level 1, Arm 1, and 26 months and 9 days for Cohort 2, Level 2, Arm 1.

Other adverse events

Additional Information

Dr. Deborah E. Citrin

National Cancer Institute

Phone: 240-760-6206

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place