Clinical trial NCT03253744: Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy
Official title: Phase I Trial of Image Guided Focally Dose Escalated Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Prostatic Neoplasm
Keywords: Image Guidance
Dose Escalation
Radiotherapy
Re-irradiation
Quality of Life
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2017-08-18
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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....

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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 3 weeks post-treatment
Secondary outcomes:
measure: 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
timeFrame: 6 months after radiation
measure: 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
timeFrame: 6 months after radiation
measure: Changes of Sexual Health Inventory for Men (SHIM) Quality of Life (QOL) Scores During and After Treatment
timeFrame: Baseline compared to 24 months after treatment
measure: Changes of American Urologic Association (AUA) Symptom Index Quality of Life (QOL) Scores During and After Treatment
timeFrame: Baseline compared to 24 months after treatment
measure: Changes of Expanded Prostate Cancer Index Composite (EPIC-26) Quality of Life (QOL) Scores During and After Treatment
timeFrame: Baseline compared to 24 months after treatment
measure: Biochemical Progression Free Survival (bPFS)
timeFrame: 1 and 2 years after treatment
measure: Dose Limiting Toxicities (DLT)
timeFrame: 3 weeks after end of treatment
Other outcomes:
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
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.
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Deborah E Citrin, M.D.
role: PRINCIPAL_INVESTIGATOR
References: