Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy
- Conditions
- Prostate CancerCancer Of ProstateProstate NeoplasmsProstatic CancerNeoplasms of Prostate
- Interventions
- Radiation: Prostate bed with integrated boostRadiation: Prostate bed irradiation onlyDiagnostic Test: Whole Body Bone ScanDiagnostic Test: 18F-NaF PET ImagingDiagnostic Test: CTDiagnostic Test: mpMRI
- Registration Number
- NCT03388619
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1/Prostate Bed with Integrated Boost Whole Body Bone Scan Prostate bed with integrated boost. Arm 1/Prostate Bed with Integrated Boost Prostate bed with integrated boost Prostate bed with integrated boost. Arm 1/Prostate Bed with Integrated Boost 18F-NaF PET Imaging Prostate bed with integrated boost. Arm 1/Prostate Bed with Integrated Boost CT Prostate bed with integrated boost. Arm 1/Prostate Bed with Integrated Boost mpMRI Prostate bed with integrated boost. Arm 2/Prostate Bed Irradiation Only Prostate bed irradiation only Prostate bed irradiation only. Arm 2/Prostate Bed Irradiation Only Whole Body Bone Scan Prostate bed irradiation only. Arm 2/Prostate Bed Irradiation Only 18F-NaF PET Imaging Prostate bed irradiation only. Arm 2/Prostate Bed Irradiation Only CT Prostate bed irradiation only. Arm 2/Prostate Bed Irradiation Only mpMRI Prostate bed irradiation only. Arm 1/Prostate Bed with Integrated Boost ADT Prostate bed with integrated boost. Arm 2/Prostate Bed Irradiation Only ADT Prostate bed irradiation only.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Fractions 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.
Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Gray (Gy) 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.
- Secondary Outcome Measures
Name Time Method Grade 2-5 Serious and/or Non-serious Adverse Events Unlikely, Probably, Possibly and Definitely Attributable to Research 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.
Biochemical Progression Free Survival (bPFS) 1 and 2 years after treatment 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.
American Urologic Association Symptom Index Score (AUA-SI) 2 years after treatment The AUA-SI is used to measure radiation morbidity and to make treatment decisions.
Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety Short Form (SF) 4a: 2 years after treatment 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).
Decision Regret Scale (DRS) 2 years after treatment 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).
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Short Form (SF) 4a: 2 years after treatment 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.
Proportion of Participants That Have Improvement in Quality of Life After Treatment 1 and 2 years 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.
Sexual Health Inventory for Men (SHIM) 2 years after treatment Participants completed a 6-question questionnaire to assess erectile dysfunction.
Patient-Reported Outcomes Measurement Information System (PROMIS) - Psychosocial Impact Positive Short Form (SF) 4a 2 years after treatment Participants complete a form to assess positive psychosocial (emotional and social) outcomes of illness.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States