ABlative Radiotherapy (for) Unfavorable Prostate Tumors

Prostate Cancer Clinical Trial

— ABRUPT  

Official title:

Single-Dose Image-Guided Radiotherapy (IGRT) With Focal Boost to the MRI-defined Macroscopic Tumor Volume for Intermediate Unfavorable and High Risk Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04831983
• Other study ID #: ABRUPT
• Status: Recruiting
• Start date: April 15, 2021
• Est. completion date: April 1, 2029

Study information

• Verified date: January 2024
• Source: University of Milano Bicocca
• Contact: STEFANO ARCANGELI, MD
• Phone: +39 039-2333663
• Email: stefano.arcangeli[@]unimib.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Published clinical evidence confirms that a single dose of 24 Gy provides unprecedented long-term local control in primary and metastatic prostate cancer with safe toxicity profiles, provided that exposure of surrounding healthy tissues is critically assessed with fulfillment of strict constraints and dose distribution is accomplished using image guidance and tracking tools. In the present trial, intermediate unfavorable and selected high-risk organ-confined prostate cancer patients will undergo Single Dose Radiation Therapy (SDRT) With Focal Boost to the MRI-defined Macroscopic Tumor Volume by means of image-guided volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) and state-of-the-art treatment-planning and quality assurance procedures. Androgen Deprivation Therapy (ADT) type and duration has been set as per standard of care, in accordance with current recommendations and guidelines.

Description:

Patients enrolled in this observational prospective trial will be offered image-guided, volumetric modulated radiotherapy (IGRT-VMAT) in a single session (SDRT) of 21 Gy to the whole gland with a simultaneous boost of 24 Gy to the macroscopic PI-RADS driven (4-5) tumour(s). ADT will be prescribed concomitantly, as per standard of care. A real time non-ionizing prostate monitoring will be used to account for intra-fractional errors. If the dose constraints to the normal tissues are at risk, these will be prioritised over the aimed boost dose. The primary endpoint of the trial is 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 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, IPSS, ICIQ-SF) at various timepoints. Percentage or total mean score will be reported according 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: April 1, 2029
• Est. primary completion date: April 1, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 90 Years

Eligibility

INCLUSION CRITERIA

• Histologically proven prostate adenocarcinoma;
• Intermediate and High risk disease, as per the NCCN definition;
• N0M0 at staging with standard techniques (Bone Scan and Abdominal CT) or (preferably) Choline or PSMA PET-CT;
• ECOG performance status between 0 and 2;
• Life expectancy of > 5 years, in the opinion of the investigator;
• IPSS score must be = 19 (alpha blockers allowed);

EXCLUSION CRITERIA:

• =T3b disease according to the 8th AJCC classification;
• PSA>20 ng/ml at any time point;
• Previous local treatment of the prostate with surgery (radical prostatectomy or cryotherapy);
• Previous radiotherapy to the pelvis;
• Previous invasive malignancy unless disease free for a minimum of 5 years;
• Active Crohn's Disease or Ulcerative Colitis;

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
Italy	Radiation Oncology, ASST Monza (University of Milan Bicocca)	Monza	MB

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Bodo S, Campagne C, Thin TH, Higginson DS, Vargas HA, Hua G, Fuller JD, Ackerstaff E, Russell J, Zhang Z, Klingler S, Cho H, Kaag MG, Mazaheri Y, Rimner A, Manova-Todorova K, Epel B, Zatcky J, Cleary CR, Rao SS, Yamada Y, Zelefsky MJ, Halpern HJ, Koutcher — View Citation

Brand DH, Tree AC, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Henderson D, Brown S, Cruickshank C, Burnett S, Duffton A, Griffin C, Hinder V, Morrison K, N — View Citation

Foerster R, Zwahlen DR, Buchali A, Tang H, Schroeder C, Windisch P, Vu E, Akbaba S, Bostel T, Sprave T, Zamboglou C, Zilli T, Stelmes JJ, Telkhade T, Murthy V. Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review. Cancers (Bas — View Citation

Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, Gharzai LA, Jaworski EM, Mehra R, Hearn JWD, Morgan TM, Salami SS, Cooperberg MR, Mahal BA, Soni PD, Kaffenberger S, Nguyen PL, Desai N, Feng FY, Zumsteg ZS, Spratt DE. Stereotactic Body Radi — View Citation

Lukka HR, Pugh SL, Bruner DW, Bahary JP, Lawton CAF, Efstathiou JA, Kudchadker RJ, Ponsky LE, Seaward SA, Dayes IS, Gopaul DD, Michalski JM, Delouya G, Kaplan ID, Horwitz EM, Roach M 3rd, Pinover WH, Beyer DC, Amanie JO, Sandler HM, Kachnic LA. Patient Re — View Citation

Macias VA, Barrera-Mellado I. Ultra-hypofractionated radiation therapy for unfavourable intermediate-risk and high-risk prostate cancer is safe and effective: 5-year outcomes of a phase II trial. BJU Int. 2020 Feb;125(2):215-225. doi: 10.1111/bju.14925. E — 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

Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M, Kindblom J, Ginman C, Johansson B, Bjornlinger K, Seke M, Agrup M, Fransson P, Tavelin B, Norman D, Zackrisson B, Anderson H, Kjellen E, Franzen L, Nilsson P. Ultra-hypofr — View Citation

Zelefsky MJ, Greco C, Motzer R, Magsanoc JM, Pei X, Lovelock M, Mechalakos J, Zatcky J, Fuks Z, Yamada Y. Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases — 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 gastrointestinal (GI) and genitourinary (GU) toxicity for patients who undergo SD RT with focal boost on dominant lesion(s) for intermediate unfavorable and selected high risk organ-confined prostate cancer.	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 erectile dysfunction assessed by International Index of Erectile Function Questionnaire ranging from 5 (worst ) to 25 (best)	To assess erectile function after SDRT using IIEF 5	60 months
Secondary	Number of participants with voiding symptoms assessed by International Prostatic Symptoms Score (IPSS), ranging from 0 (best) to 35 (worst)	To assess voiding symptoms after SDRT using IPSS	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 SDRT using ICIQ-SF	60 months
Secondary	Number of participants with biochemical relapse assessed by PSA (Phoenix definition)	To assess biochemical outcome after SDRT using serum PSA levels	60 months