ABlative Radiotherapy (for) Unfavorable Prostate Tumors

Официальное название

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

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 [Срок оценки: 60 months]

Вторичные конечные точки (5)

• 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 [Срок оценки: 60 months]
• Number of participants with erectile dysfunction assessed by International Index of Erectile Function Questionnaire ranging from 5 (worst ) to 25 (best) [Срок оценки: 60 months]
• Number of participants with voiding symptoms assessed by International Prostatic Symptoms Score (IPSS), ranging from 0 (best) to 35 (worst) [Срок оценки: 60 months]
• Number of participants with urinary incontinence assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), ranging from 0 (best) to 21 (worst) [Срок оценки: 60 months]
• Number of participants with biochemical relapse assessed by PSA (Phoenix definition) [Срок оценки: 60 months]

Критерии участия

Критерии включения

• 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);

Критерии исключения

• ≥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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• Radiation Oncology, ASST Monza (University of Milan Bicocca) — Monza

Публикации

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• 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 Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. Int J R PMID 30959121
• 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 Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2018 PMID 29913254
• 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 ASTRO, ASCO, and AUA Evidence-Based Guideline. J Clin Oncol. 2018 Oct 11;36(34):JCO1801097. doi: 10.1200/JCO.18.01097. Online ahead of print. No a PMID 30307776
• 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. Epub 2019 Nov 8. PMID 31614071

Идентификаторы

NCT: NCT04831983 · ABRUPT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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