POst-Prostatectomy Ablative Radiation Therapy

Radiation Toxicity Clinical Trial

— POPART  

Official title:

POst-Prostatectomy Ablative Radiation Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04831970
• Other study ID #: POPART
• Status: Recruiting
• Start date: April 15, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2022
• Source: University of Milano Bicocca
• Contact: Stefano Arcangeli, MD
• Phone: +39-0392333663
• Email: stefano.arcangeli[@]unimib.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The use of hypofractionated radiotherapy for prostate cancer has matured to a point that in current guidelines extremely hypofractionated image-guided IMRT regimens (6 Gy per fraction or greater) can be considered an alternative to conventionally fractionated regimens at clinics with appropriate technology, physics and clinical expertise. The delivery of fewer and larger fractions with hypofractionation compared to conventional radiotherapy might effectively improve the therapeutic ratio while maintaining isoeffective tumour doses, thus, shortening overall treatment time. In the present study, patients will undergo postoperative image-guided SBRT by means of volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance procedures. Normal tissue sparing and delivery accuracy are accomplished by the use of devices that ensure stability and beam location reproducibility. The primary endpoint is to evaluate the cumulative incidence of treatment related toxicities and adverse events in the acute (< 90 days from the end of treatment) and late (> 90 days) setting.

Description:

In this observational prospective trial eligible patients are those with adverse pathological features or rising PSA after radical prostatectomy proposed for receiving 31 Gy in 5 sessions each of 6.2 Gy to the prostatic bed delivered in one week, and up to 32.5 Gy in 5 sessions each of 6.5 Gy delivered in one week, respectively, in case of clinical relapse.

Patients will be treated by means of image guided volumetric modulated radiotherapy (IGRT-VMAT). A real time non-ionizing target monitoring might be used to account for intra-fractional errors, if deemed appropriate. Whether the dose constraints to the normal tissues are at risk, these will be prioritised over the prescription dose to the target. The primary endpoint of the trial is to assess the treatment related toxicity measured by the CTCAE v5.0. Secondary endpoints are quality of life in different domains (sexual, rectal , urinary) and biochemical outcome.

Patients will be followed at approximately one month, then every 3 months for the first 12 months and every 6 months thereafter. Quality of Life will be prospectively evaluated through validated tools (ECOG, EPIC, IIEF-5, ICIQ-SF) at various timepoints. Percentage or total mean score will be reported according to the questionnaires, whether they grade values in a scale or use descriptive statistics. Kaplan-Meier curve analysis of biochemical relapse free survival (b-RFS) at 2 and 5-year bRFS for all patients will be estimated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 90 Years

Eligibility

INCLUSION CRITERIA

• Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy).

• Pathologic T3N0/Nx disease or pathologic T2N0/Nx disease, with or without a positive prostatectomy surgical margin

• Post-radical prostatectomy PSA of = 0.1 - < 2.0 ng/mL.

• Clinical local relapse assessed by Magnetic Resonance Imaging (MRI) of the pelvis

• ECOG performance status of 0-1

• No distant metastases at restaging (in case of biochemical failure), within 60 days prior to registration

• Patients can be on androgen deprivation therapy

• Ability to understand and willingness to sign a study-specific informed consent prior to study entry

EXCLUSION CRITERIA

• N1 and or M1 patients

• Prior radiation of any kind to the prostate gland or pelvis

• Prior brachytherapy is not allowed

• History of inflammatory colitis or other active severe comorbidities

• Patients who are on immunosuppressant medication

Related Conditions & MeSH terms

• Radiation Toxicity

Locations

Country	Name	City	State
Italy	Radiation Oncology, ASST Monza (University of Milan Bicocca)	Monza
Italy	Radiation Oncology, Humanitas Cancer Center (Humanitas University)	Rozzano	MI

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Ballas LK, Luo C, Chung E, Kishan AU, Shuryak I, Quinn DI, Dorff T, Jhimlee S, Chiu R, Abreu A, Jennelle R, Aron M, Groshen S. Phase 1 Trial of SBRT to the Prostate Fossa After Prostatectomy. Int J Radiat Oncol Biol Phys. 2019 May 1;104(1):50-60. doi: 10. — View Citation

Bell LJ, Eade T, Hruby G, Bromley R, Kneebone A. Intra-fraction displacement of the prostate bed during post-prostatectomy radiotherapy. Radiat Oncol. 2021 Jan 22;16(1):20. doi: 10.1186/s13014-020-01743-9. — View Citation

Cuccia F, Mortellaro G, Serretta V, Valenti V, Tripoli A, Gueci M, Luca N, Lo Casto A, Ferrera G. Hypofractionated postoperative helical tomotherapy in prostate cancer: a mono-institutional report of toxicity and clinical outcomes. Cancer Manag Res. 2018 — View Citation

Koerber SA, Katayama S, Sander A, Jaekel C, Haefner MF, Debus J, Herfarth K. Prostate bed irradiation with alternative radio-oncological approaches (PAROS) - a prospective, multicenter and randomized phase III trial. Radiat Oncol. 2019 Jul 10;14(1):122. d — View Citation

Kruser TJ, Jarrard DF, Graf AK, Hedican SP, Paolone DR, Wegenke JD, Liu G, Geye HM, Ritter MA. Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence. Cancer. 2011 Jun 15;117(12):2629-36. doi: 10.1002/cncr.25824. Epub 201 — View Citation

Lewis SL, Patel P, Song H, Freedland SJ, Bynum S, Oh D, Palta M, Yoo D, Oleson J, Salama JK. Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):605-11. — View Citation

Morgan SC, Hoffman K, Loblaw DA, Buyyounouski MK, Patton C, Barocas D, Bentzen S, Chang M, Efstathiou J, Greany P, Halvorsen P, Koontz BF, Lawton C, Leyrer CM, Lin D, Ray M, Sandler H. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An A — View Citation

Wages NA, Sanders JC, Smith A, Wood S, Anscher MS, Varhegyi N, Krupski TL, Harris TJ, Showalter TN. Hypofractionated Postprostatectomy Radiation Therapy for Prostate Cancer to Reduce Toxicity and Improve Patient Convenience: A Phase 1/2 Trial. Int J Radia — View Citation

Wong GW, Palazzi-Churas KL, Jarrard DF, Paolone DR, Graf AK, Hedican SP, Wegenke JD, Ritter MA. Salvage hypofractionated radiotherapy for biochemically recurrent prostate cancer after radical prostatectomy. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):4 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0	To assess treatment related acute (< 90 days from the end of treatment) and late (> 90 days) gastrointestinal (GI) and genitourinary (GU) toxicity in patients who undergo postoperative SBRT using CTCAE v.5.0	60 months
Secondary	QUALITY OF LIFE (QOL) assessed by Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire. For each domain minimum symptom score (=0) means best QOL and maximum symptom score (=12) means worst QOL	To measure symptom scores for each QOL domain (urinary incontinence, urinary irritative/obstructive, bowel, sexual) after SDRT by EPIC-26 Questionnaire	60 months
Secondary	Number of participants with urinary incontinence assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), ranging from 0 (best) to 21 (worst)	To assess urinary continence after postoperative SBRT using ICIQ-SF	60 months
Secondary	Number of participants with erectile dysfunction assessed by International Index of Erectile Function Questionnaire ranging from 5 (worst ) to 25 (best)	To assess erectile function after postoperative SBRT using IIEF 5	60 months
Secondary	Number of participants with biochemical relapse assessed by PSA (cut off 0.20 ng/mL)	To assess biochemical outcome after postoperative SBRT using serum PSA levels	60 months