Clinical trial NCT03388619: Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy
Official title: A Phase I Trial of Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Cancer Of Prostate
Prostate Neoplasms
Prostate Cancer
Neoplasms of Prostate
Prostatic Cancer
Keywords: Rising PSA
No evidence of metastatic disease
Entire Prostate Bed
Quality of Life
Irradiation
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-01-03
Enrollment: 30
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:

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.

Eligibility criteria: * 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)

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Gray (Gy)
timeFrame: 3 weeks after radiation
measure: Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Fractions
timeFrame: 3 weeks after radiation
Secondary outcomes:
measure: Biochemical Progression Free Survival (bPFS)
timeFrame: 1 and 2 years after treatment
measure: Proportion of Participants That Have Improvement in Quality of Life After Treatment
timeFrame: 1 and 2 years after treatment
measure: Sexual Health Inventory for Men (SHIM)
timeFrame: 2 years after treatment
measure: American Urologic Association Symptom Index Score (AUA-SI)
timeFrame: 2 years after treatment
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Short Form (SF) 4a:
timeFrame: 2 years after treatment
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety Short Form (SF) 4a:
timeFrame: 2 years after treatment
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Psychosocial Impact Positive Short Form (SF) 4a
timeFrame: 2 years after treatment
measure: Decision Regret Scale (DRS)
timeFrame: 2 years after treatment
measure: Grade 2-5 Serious and/or Non-serious Adverse Events Unlikely, Probably, Possibly and Definitely Attributable to Research
timeFrame: 3 weeks after radiation
Other outcomes:
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
timeFrame: Date treatment consent signed to date off study, an average of 25 months
measure: Number of Participants With a Dose-limiting Toxicity (DLT)
timeFrame: 3 weeks after radiation
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:
citation: 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.
citation: 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.
citation: 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.