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

August 7, 2026 updated by: Deborah Citrin, M.D., National Cancer Institute (NCI)

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

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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)
Time Frame: 3 weeks after radiation
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
Time Frame: 3 weeks after radiation
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
Grade 2-5 Serious and/or Non-serious Adverse Events Unlikely, Probably, Possibly and Definitely Attributable to Research
Time Frame: 3 weeks after radiation
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
Biochemical Progression Free Survival (bPFS)
Time Frame: 1 and 2 years after treatment
bPFS is defined as the percent of participants without evidence of (prostate-specific antigen) PSA progression or death. PSA progression (also known as biochemical failure) is defined based on elevation of PSA above 0.1 ng/dL. Kaplan-Meier survival analysis will be used to report bPFS.
1 and 2 years after treatment
Changes in Erectile Dysfunction QOL Scores During and After Treatment Measured by the Sexual Health Inventory for Men (SHIM)
Time Frame: Baseline compared to 24 months after treatment
Changes before and after treatment with prostate bed radiation in participant reported outcomes (Sexual Health Inventory for Men (SHIM). The QOL scores will be summarized at baseline and after treatment. 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.
Baseline compared to 24 months after treatment
Changes of American Urologic Association (AUA) Symptom Index Quality of Life (QOL) Scores During and After Treatment
Time Frame: Baseline compared to 24 months after treatment
Changes of QOL scores during and after treatment with prostate bed radiation in American Urologic Association (AUA) Symptom Index. 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 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.
Baseline compared to 24 months after treatment
Changes of Expanded Prostate Cancer Index Composite (EPIC-26) Quality of Life (QOL) Scores During and After Treatment
Time Frame: Baseline compared to 24 months after treatment
Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy on participant(pt) reported outcomes, EPIC-26 in pts 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 pt-specific trajectory of QOL scores. The EPIC-26 is a shortened, validated questionnaire used to assess health related QOL in individuals with prostate cancer. EPIC26 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. EPIC26 uses a Likert scale for each item, and scores are transformed to a 0-100 scale, with higher scores indicating better HRQOL.
Baseline compared to 24 months 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)
Time Frame: Date treatment consent signed to date off study, an average of 25 months
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)
Time Frame: 3 weeks after radiation
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

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 7, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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