Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy

A Phase I Trial of Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy

Background:

Sometimes prostate cancer comes back after a person's prostate is removed. In this case, radiation is a common treatment. Radiation kills prostate cancer cells. It can be very effective. It is usually given in short doses almost every day for 6 or 7 weeks. Researchers want to see if a shorter schedule can be as effective. They want to see if that causes the same or fewer side effects. Usually, radiation is used to treat the entire area where the prostate was before surgery. In some patients, an area of tumor can be seen on scans. Researchers are also trying to see if they can give less dose to the area usually treated with radiation if the full dose is given to the tumor seen on scans.

Objective:

To find the shortest radiation schedule that people can tolerate without strong side effects.

Eligibility:

People at least 18 years old who have had a prostatectomy and will get radiation.

Design:

Participants will be screened with:

• Medical history
• Physical exam
• Blood and urine tests
• Scan that uses a small amount of radiation to make a picture of the body
• Scan that uses a magnetic field to make an image of the body
• Participants will provide documents that confirm their diagnosis.
• Participants may have a scan of the abdomen and pelvis.

Before they start treatment, participants will have another physical exam and blood tests.

Participants will get radiation each day Monday through Friday. Treatment may last 2, 3, or 4 weeks.

Participants may provide a tissue sample from a previous procedure for research.

Participants will answer questions about their general well-being and function.

About 4-5 weeks after they finish radiation treatment, participants will have a follow-up visit. They will be examined and give a blood sample. They will have 6 follow-up visits for the next 2 years.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Neoplasms of Prostate; Cancer Of Prostate; Prostate Neoplasms; Prostatic Cancer
• Intervention / Treatment: Radiation: Prostate bed with integrated boost; Diagnostic test: Whole Body Bone Scan; Diagnostic test: 18F-NaF PET Imaging; Diagnostic test: CT; Diagnostic test: mpMRI; Drug: ADT; Radiation: Prostate bed irradiation only

Detailed Description

BACKGROUND:

Prostate cancer that recurs after prostatectomy (rising prostate-specific antigen (PSA) with no evidence of metastatic disease is often treated with radiation to the entire prostate bed to a dose of 66-72 Gray (Gy) over 6-7 weeks. This treatment can provide PSA control in approximately 75% of patients but may have associated genitourinary and gastrointestinal toxicity due to irradiation of the rectum, small bowel, and bladder. Imaging of prostate cancer has improved to the extent that recurrent disease is often identified in the prostate bed or in other pelvic sites. The current standard is to irradiate the entire prostate bed to the total dose. This trial will test the tolerability of accelerated treatment designed to yield a similar rate of late toxicity. In addition, in patients with visible tumor, it will test the feasibility of delivering a lower dose to the prostate bed and an integrated boost (simultaneous) to the visible tumor to allow a higher dose to visible tumor than can be delivered with standard approaches.

OBJECTIVE:

- Define the maximum tolerated dose (MTD) hypofractionation of image guided, focally dose escalated post-prostatectomy radiation.

ELIGIBILITY:

• PSA recurrence after prostatectomy or indications for adjuvant radiation after prostatectomy.
• No evidence of distant metastases of prostate cancer (pelvic lymph nodes are allowed).
• Age greater than or equal to 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

DESIGN:

This is a Phase I trial of hypofractionated focal dose escalation with reduced dose prostate bed irradiation using image and pathologic guidance. The prostate bed will be treated with hypofractionated radiation and areas in the prostate bed or pelvis shown to have tumor on biopsy or with advanced imaging studies will be treated with an integrated boost to visible tumor. The treatment duration will be decreased sequentially in three Dose Level groups. Quality of life and functional outcomes such as urine, bowel, and erectile function will be assessed with questionnaires. A maximum of 48 patients will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

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 or cytologically confirmed adenocarcinoma of the prostate.

• Indications for post-prostatectomy radiation exist:

  • Disease progression (detectable prostate-specific antigen (PSA) on two measurements obtained at least one month apart) or
  • indications for adjuvant radiation exist (if undetectable PSA): pathologic T3, T4, N+ disease or positive margins (within 1 year of prostatectomy).
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 60)
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Radiation is teratogenic; thus, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and up to 120 days after the last radiation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
• Human immunodeficiency virus (HIV) positive patients are included if CD4+ (cytotoxic T cells) T-cell count > 200 cells/uL; on stable antiretroviral therapy for > 1 year with HIV viral load <200 copies/mL, and no history of opportunistic infections in > 1 year.

EXCLUSION CRITERIA:

• Patients who are receiving any other investigational agents concurrently.
• Documented metastases of prostate cancer outside of the pelvis (pelvic lymph nodes are allowed only if within the prostate bed region).
• History of radiation that would overlap with the intended treatment to the prostate bed.
• Known contraindications to radiation such as inflammatory bowel disease, active systemic lupus or scleroderma, or radiation hypersensitivity syndrome (Ataxia Telangiectasia or Fanconi's Anemia)
• Subjects with any coexisting medical or psychiatric condition which, in the opinion of the Investigator likely to interfere with study procedures and/or results.
• Medically indicated use of known radiosensitizing drugs (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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1/Prostate Bed with Integrated Boost; Prostate bed with integrated boost.	Radiation: Prostate bed with integrated boost; Radiation will be delivered at an escalated dose to areas of recurrent prostate cancer identified on imaging and a reduced dose will be delivered to the entire prostate bed.; Diagnostic test: Whole Body Bone Scan; At screening, if required by clinician.; Diagnostic test: 18F-NaF PET Imaging; At screening, if required by clinician.; Other Names: Fluorine 18-sodium fluoride positron emission tomography; Diagnostic test: CT; Computed tomography of the abdomen and pelvis if clinically indicated at screening, with oral and intravenous contrast.; Other Names: Computed tomography; Diagnostic test: mpMRI; mpMRI of the prostate bed at screening and 6 month follow up.; Other Names: Multiparametric magnetic resonance imaging; Drug: ADT; After enrollment if clinically indicated (i.e., anti-androgen, gonadotropin releasing hormone agonist, or combination of both).; Other Names: androgen deprivation therapy
Experimental: Arm 2/Prostate Bed Irradiation Only; Prostate bed irradiation only.	Diagnostic test: Whole Body Bone Scan; At screening, if required by clinician.; Diagnostic test: 18F-NaF PET Imaging; At screening, if required by clinician.; Other Names: Fluorine 18-sodium fluoride positron emission tomography; Diagnostic test: CT; Computed tomography of the abdomen and pelvis if clinically indicated at screening, with oral and intravenous contrast.; Other Names: Computed tomography; Diagnostic test: mpMRI; mpMRI of the prostate bed at screening and 6 month follow up.; Other Names: Multiparametric magnetic resonance imaging; Drug: ADT; After enrollment if clinically indicated (i.e., anti-androgen, gonadotropin releasing hormone agonist, or combination of both).; Other Names: androgen deprivation therapy; Radiation: Prostate bed irradiation only; Radiation will be delivered to the prostate bed only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Gray (Gy)	Maximum tolerated dose (MTD) of image guided hypofractionated, focally dose escalated post-prostatectomy radiation is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of treatment. A DLT is defined as any of the following: 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 radiation that does not resolve to Grade 2 or less within 4 days with appropriate medical management. And delays of more than one week in completing radiation treatment due to toxicity.	3 weeks after radiation
Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Fractions	Maximum tolerated dose (MTD) of image guided hypofractionated, focally dose escalated post-prostatectomy radiation is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of treatment. A DLT is defined as any of the following: 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 radiation that does not resolve to Grade 2 or less within 4 days with appropriate medical management. And delays of more than one week in completing radiation treatment due to toxicity.	3 weeks after radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Progression Free Survival (bPFS)	bPFS is defined as the duration of time from start of treatment to time of prostate-specific antigen (PSA) progression or death, whichever occurs first. PSA progression (also known as biochemical failure) is defined based on elevation of PSA beyond 0.1 ng/dL. Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model.	1 and 2 years after treatment
American Urologic Association Symptom Index Score (AUA-SI)	The AUA-SI is used to measure radiation morbidity and to make treatment decisions.	2 years after treatment
Patient-Reported Outcomes Measurement Information System (PROMIS) - Psychosocial Impact Positive Short Form (SF) 4a	Participants complete a form to assess positive psychosocial (emotional and social) outcomes of illness.	2 years after treatment
Decision Regret Scale (DRS)	The DRS is a 5-item scale measuring distress or remorse after a health case decision. The score correlated with satisfaction with the decision (r=-0.40 to -0.60), decisional conflict (r=0.31 to 0.52), and overall rated quality of life (r=-0.25 to -0.27).	2 years after treatment
Grade 2-5 Serious and/or Non-serious Adverse Events Unlikely, Probably, Possibly and Definitely Attributable to Research	Grade 2-5 serious and/or non-serious adverse events attributable to protocol treatment. 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. Grade 2 is moderate. Grade 3 is serious. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.	3 weeks after radiation
Changes in Quality of Life (QOL) Scores After Treatment	The quality-of-life 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 quality-of-life scores.	baseline, 1 and 2 years after treatment
Changes in Erectile Dysfunction After Treatment Measured by the Sexual Health Inventory for Men (SHIM)	Participants completed a 6-question SHIM questionnaire to assess erectile dysfunction following radiation.	2 years after treatment
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Short Form (SF) 4a:	Following radiation, participants complete a form to assess negative mood (i.e., sadness, guilt), views of self (i.e., self-criticism, worthlessness) social cognition (loneliness, interpersonal alienation), decreased positive effect, and decreased engagement (loss of interest, meaning, and purpose) and are scored using item-level calibrations.	2 years after treatment
Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety Short Form (SF) 4a:	Participants complete a form and rate anxiety such as fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness) after radiation.	2 years after 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 v4.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). 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, an average of 25 months
Number of Participants With a Dose-limiting Toxicity (DLT)	A DLT is defined as any of the following: 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 radiation that does not resolve to Grade 2 or less within 4 days with appropriate medical management. And delays of more than one week in completing radiation treatment due to toxicity.	3 weeks after radiation

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Shaikh T, Li T, Handorf EA, Johnson ME, Wang LS, Hallman MA, Greenberg RE, Price RA Jr, Uzzo RG, Ma C, Chen D, Geynisman DM, Pollack A, Horwitz EM. Long-Term Patient-Reported Outcomes From a Phase 3 Randomized Prospective Trial of Conventional Versus Hypofractionated Radiation Therapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys. 2017 Mar 15;97(4):722-731. doi: 10.1016/j.ijrobp.2016.12.034. Epub 2016 Dec 28.
• Christie DR, Sharpley CF, Bitsika V. Why do patients regret their prostate cancer treatment? A systematic review of regret after treatment for localized prostate cancer. Psychooncology. 2015 Sep;24(9):1002-11. doi: 10.1002/pon.3776. Epub 2015 Mar 1.
• Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O'Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016 Aug;17(8):1047-1060. doi: 10.1016/S1470-2045(16)30102-4. Epub 2016 Jun 20.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2018
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): December 4, 2025

Study Registration Dates

• First Submitted: December 30, 2017
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Quality of Life; Irradiation; Rising PSA; No evidence of metastatic disease; Entire Prostate Bed
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Diagnostic Techniques and Procedures; Diagnosis; Pharmacologic Actions; Chemical Actions and Uses; Tomography; Diagnostic Imaging; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Magnetic Resonance Imaging; Androgen Antagonists; Tomography, X-Ray Computed; Multiparametric Magnetic Resonance Imaging
• Other Study ID Numbers: 180028; 18-C-0028

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: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No