Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy

Phase I Trial of Image Guided Focally Dose Escalated Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy

Background:

Prostate cancer is the second leading cause of cancer death in United States (U.S.) men. Radiation is an effective treatment for most patients with localized prostate cancer, but sometimes the tumor returns. Researchers want to see if a highly focused type of radiation can help. It is given in only 5 treatments. It is called stereotactic body radiation therapy (SBRT).

Objective:

To study the maximum tolerated dose and side effects of stereotactic body radiation therapy in people with a local recurrence of prostate cancer after radiation.

Eligibility:

Men at least 18 years old who have recurrent prostate cancer after radiation therapy and no evidence of distant metastatic disease.

Design:

Participants will be screened with blood tests, physical exam, and medical history. They may also have:

Magnetic resonance imaging (MRI) scan of the prostate.

Positron emission tomography (PET)/computed tomography (CT) scan. Participants will get an injection of 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) for the PET scan. They will lie very still on their back on the scanner table.

Small samples of prostate tumor tissue will be taken by a needle through the skin or rectum to see if the cancer is in the prostate. Small metal seeds will be placed into the prostate at the same time to help guide the radiation.

About 2 weeks later, participants will have a radiation treatment planning CT scan.

Participants will answer questions about their urine function, bowel function, erectile function, and mood.

Participants will receive SBRT. They will have 5 radiation treatments over 2 weeks.

Participants will have follow-up visits. They will have a physical exam, blood tests, and questionnaires.

Six months after ending SBRT, the 18F-DCFPyL PET/CT will be repeated.

Participants will continue to have routine visits until two years after treatment is completed....

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; Prostatic Neoplasm
• Intervention / Treatment: Drug: 18F-DCFPyL; Radiation: Tumor Irradiation; Radiation: Tumor Irradiation; Radiation: Prostate + tumor irradiation

Detailed Description

Background:

• Prostate cancer that recurs after prior radiation treatment can be challenging to cure due to the side effects of available treatments such as surgery and cryoablation.
• Re-irradiation with brachytherapy or stereotactic approaches has shown excellent rates of prostate cancer disease control with tolerable side effects.
• Using image guidance to allow highly conformal focal re-irradiation may potentially increase the efficacy of re-irradiation.

Objectives:

-Define the maximum tolerated dose (MTD) of image guided, focally dose escalated prostate radiation with stereotactic body radiation therapy (SBRT) in patients with a local recurrence of prostate cancer after prior radiotherapy.

Eligibility:

• Histological confirmation of recurrent prostate cancer after prior irradiation (external beam or brachytherapy)
• No evidence of distant metastases of prostate cancer
• No prior prostatectomy
• Subject is greater than or equal to18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).

Design:

• This is a Phase I trial of focal dose escalation with SBRT using image and pathologic guidance.
• Areas in the prostate shown to have tumor on biopsy or with advanced imaging studies will be treated with highly conformal SBRT over a period of two to three weeks. Treatment will be guided and gated by fiducials implanted in the prostate.
• Patients will be treated to escalating doses based on tolerability of the treatment.
• Quality of life and functional outcomes such as urine, bowel, and erectile function will be assessed with questionnaires.
• Up to 52 patients will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Theresa Cooley-Zgela, R.N.; Phone Number: (240) 764-6207; Email: theresa.cooleyzgela@nih.gov
• Study Contact Backup: Name: Deborah E Citrin, M.D.; Phone Number: (240) 760-6206; Email: citrind@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:
• Patients must have histologically confirmed locally recurrent adenocarcinoma of the prostate after prior radiation (external beam radiation therapy (EBRT) or brachytherapy).
• Prostate-specific antigen (PSA) failure after definitive radiation as defined by the Phoenix criteria (PSA elevation at least 2 nanograms (ng) per deciliter (dL) above post-radiotherapy nadir)
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

• Patients who are receiving any other investigational agents.
• PSA greater than or equal to 20 ng/dL if no prior 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) scan obtained (If PSA > 20 and 18F-DCFPyL obtained within 3 months prior to enrollment shows no evidence of metastatic disease, subjects may be included in the study)
• Biochemical recurrence within one year of completion of radiotherapy
• Need for chronic anticoagulation therapy (chronic low dose aspirin is not an exclusion)
• Pre-existing and ongoing radiation-related grade 3 bowel or bladder toxicity
• Inflammatory bowel disease
• Active Lupus or Active scleroderma
• Patients with distant metastatic disease (prostate adjacent adenopathy is not an exclusion)
• Prior prostatectomy
• Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results.
• Subjects with severe claustrophobia that is unresponsive to oral anxiolytics
• Other medical conditions deemed by the Principal Investigator (or associates) to make the subject unsafe or ineligible for protocol procedures
• Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
• Serum creatinine > 2 times the upper limit of normal
• Total bilirubin > 2 times the upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin > 3.0.
• Liver transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than 3 times the upper limit of normal
• Patients with positive Human Immunodeficiency Virus (HIV) status and currently requiring treatment with agents known to sensitize to irradiation, such as protease inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Level 1, Arm 1: Tumor Irradiation; Arm 1: Tumor irradiation. Cohort 1, Level 1, Arm 1 - 40 gray (Gy) to Tumor planning target volume (PTV) Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy. 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.	Drug: 18F-DCFPyL; Participants will receive 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.; Other Names: 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid; Radiation: Tumor Irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy.; Other Names: SBRT; Radiation: Tumor Irradiation; 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.; Other Names: EBRT
Experimental: Cohort 1, Level 2, Arm 1 - Tumor Irradiation; Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV) Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate. 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.	Drug: 18F-DCFPyL; Participants will receive 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.; Other Names: 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid; Radiation: Tumor Irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy.; Other Names: SBRT; Radiation: Tumor Irradiation; 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.; Other Names: EBRT
Experimental: Cohort 2, Level 1, Arm 2 - Prostate and Tumor Irradiation; Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) PTV to Prostate and 40 Gy to Tumor planning target volume (PTV) Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate. 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.	Drug: 18F-DCFPyL; Participants will receive 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.; Other Names: 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid; Radiation: Tumor Irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy.; Other Names: SBRT; Radiation: Tumor Irradiation; 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.; Other Names: EBRT; Radiation: Prostate + tumor irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate.; Other Names: SBRT
Experimental: Cohort 2, Level 2, Arm 2 - 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 Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate. 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.	Drug: 18F-DCFPyL; Participants will receive 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.; Other Names: 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid; Radiation: Tumor Irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy.; Other Names: SBRT; Radiation: Tumor Irradiation; 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.; Other Names: EBRT; Radiation: Prostate + tumor irradiation; Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate.; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	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.	3 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	6 months after radiation
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	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.	6 months after radiation
Changes of Sexual Health Inventory for Men (SHIM) Quality of Life (QOL) Scores During and 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.	2 years after treatment
Changes of American Urologic Association (AUA) Symptom Index Quality of Life (QOL) Scores During and 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.	2 years after treatment
Changes of Expanded Prostate Cancer Index Composite (EPIC-26) Quality of Life (QOL) Scores During and After Treatment	Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes, Expanded Prostate Cancer Index Composite (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 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.	2 years after treatment
Biochemical Progression Free Survival (bPFS)	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.	1 and 2 years after treatment
Dose Limiting Toxicities (DLT)	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.	3 weeks after end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	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.	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.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Deborah E Citrin, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2018
• Primary Completion (Actual): May 3, 2023
• Study Completion (Estimated): February 16, 2025

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (Actual): August 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Quality of Life; Radiotherapy; Dose Escalation; Image Guidance; Re-irradiation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 170153; 17-C-0153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No