MRI-based Focal Intraprostatic Simultaneous Integrated Boost (SIB) Intensification With De-escalated Adaptive-risk SBRT for Patients With Low to Intermediate Risk Prostate Cancer

Официальное название

A Phase II Study of MRI-based Focal Intraprostatic SIB (Simultaneous Integrated Boost) Intensification With De-escalated Adaptive-risk SBRT for Patients With Low to Intermediate Risk Prostate Cancer

Обзор

The goal of this clinical trial is to determine the safety of stereotactic body radiation therapy (SBRT) microboost technique in patients with low to intermediate risk prostate cancer. The main question it aims to answer is: Is microboost SBRT with whole gland de-escalation both safe and effective in managing patients with low to intermediate-risk prostate cancer while maintaining acceptable toxicity levels? All patients will receive microboost SBRT at a dose of 45 Gy delivered in 5 fractions in up to 4 MRI-defined lesions. Patients (Arm 1) with highest grade disease in the microboost target lesion in the absence of GG2-3 beyond the microboost target (only GG1 disease can be present outside of the microboost region) will receive whole gland de-escalation at a dose of 30 Gy delivered in 5 fractions. Patients (Arm 2) with highest grade disease outside of the target lesion will receive whole gland de-escalation at a dose of 35 Gy delivered in 5 fractions. Participants will be treated every other day over a two week period and then follow up after radiation treament for up to 5 years. Participants will be asked to complete questionnaires and provide blood and urine samples for research purposes.

Вмешательства

• Лучевая терапия Microboost SBRT
  Microboost SBRT at a dose of 45 Gy for 5 fractions
• Лучевая терапия Whole gland de-escalation 30 Gy
  Whole gland de-escalation at a dose of 30 Gy delivered in 5 fractions.
• Лучевая терапия Whole gland de-escalation 35 Gy
  Whole gland de-escalation at a dose of 35 Gy delivered in 5 fractions

Первичные конечные точки

• Incidence of acute grade 2 or higher genitourinary toxicity [Срок оценки: during treatment through 90 days after radiation treatment]

Вторичные конечные точки (11)

• Incidence of acute grade 2 or higher gastrointestinal (GI) toxicity [Срок оценки: Up to 5 years]
• Incidence of late grade 2 or higher genitourinary (GU) or gastrointestinal (GI) toxicity [Срок оценки: Up to 5 years]
• Incidence of late grade 3 or higher genitourinary or gastrointestinal toxicity [Срок оценки: Up to 5 years]
• PSA (Prostate-specific antigen) nadir [Срок оценки: at 2 years and 5 years]
• Biochemical failure (BF) [Срок оценки: at 2 years and 5 years]
• Biochemical failure free survival (BFFS) [Срок оценки: up to 5 years]
• Disease-free survival (DFS) [Срок оценки: up to 5 years]
• Patient-reported QoL (Quality of life) outcomes- Expanded Prostate Index Composite (EPIC)-26 [Срок оценки: up to 5 years]
• Patient-reported QoL outcomes- International Prostate Symptom Score (I-PSS) [Срок оценки: up to 5 years]
• Patient-reported QoL outcomes- International Index of Erectile Dysfunction (IIEF-5) [Срок оценки: up to 5 years]
• Patient-reported QoL outcomes- Health Questionnaire (EQ-5D-5L) [Срок оценки: up to 5 years]

Критерии участия

Критерии включения

• Patients age 18 or older.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients with histologically confirmed adenocarcinoma of the prostate who have not received prior pelvic radiation therapy or prostatectomy.
• Patients with low to intermediate risk group defined by the NCCN (National Comprehensive Cancer Network) guidelines as follows:

• Low risk prostate cancer:

• cT1-cT2a (AJCC; 8TH edition, 2017)
• Grade Group 1 (GG1)
• PSA <10 ng/mL
• Intermediate risk prostate cancer:

• cT2b-cT2c (AJCC; 8TH edition, 2017)
• Grade Group 2 (GG2) or Grade Group 3 (GG3)
• PSA 10-20 ng/mL
• Patients with unfavorable intermediate risk prostate cancer defined by the NCCN guidelines are recommended to undergo a PSMA (Prostate-Specific Membrane Antigen) PET, then the PSMA PET must show localized disease.
• Patients must have preferably undergone a standard of care pretreatment MRI fusion biopsy\* to identify visible intraprostatic lesions and confirm the absence of regional or distant metastatic disease, with criteria as follows:

• Ability to undergo an MRI fusion biopsy;
• Prostate size <100 cc on any diagnostic MRI;
• Presence of a visible prostatic lesion:

• PIRADS (Prostate Imaging-Reporting and Data System) 4+ lesion, and/or
• PIRADS 3 lesion with evidence of grade group 2-3
• Less than or equal to 4 lesions in total allowed;
• Lesion may contact the capsular edge, "possible" extracapsular extension (ECE) permitted; \*MRI fusion biopsy is preferred but if the positive core is in the same region as the target on the MRI based on a systemic biopsy, the patient can be included.
• Genitourinary function with a baseline score ≤20 as defined by any pre-treatment IPSS questionnaire.
• Patients are mandated to get a fiducial placement. Optional proper rectal spacer placement is recommended as determined by the treating radiation oncologist based upon whether there is overt rectal wall invasion from the hydrogel spacer or if there is minimal to no separation of the prostate-rectal interface measured at the prostate mid-gland.
• Patients with a life expectancy of greater than 5 years as assessment by the investigator. Life expectancy can be estimated using any 1 of the following tools:

• The Social Security Administration tables: https://www.ssa.gov/OACT/STATS/table4c6.html
• The WHO's Life Tables by country: https://apps.who.int/gho/data/view.main.60000?lang=en
• The Memorial Sloan Kettering Male Life Expectancy tool: https://www.mskcc.org/nomograms/prostate
• If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information.
• Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:

• With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method, which together result in a failure rate of < 1% per year, during the treatment period and for 1 year after treatment per local and institutional guidelines. Men must refrain from donating sperm during this same period.
• With a pregnant female partner, men must remain abstinent or use a condom during the treatment period per local and institutional guidelines to avoid potential exposure to the embryo.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.
• Patients who are able to give informed consent.

Критерии исключения

• Patients with evidence of disease Grade Group 4 (GG4) or higher.
• Patients with PSA >20 ng/mL.
• Patients with evidence of clinical stage T3a+ or gross extracapsular extension on the diagnostic MRI.
• Patients who received prior or concurrent androgen deprivation therapy for prostate cancer.
• Patients with more than 4 disease foci identifiable on MRI.
• Patients with evidence of metastatic disease on imaging (e.g., bone scan, PSMA PET scan, or MRI/CT scan).
• Patients with ineligibility to undergo an MRI due to:

• The presence of a cardiac pacemaker, defibrillator, or other implanted metallic or electronic device which is considered MRI unsafe;
• Severe claustrophobia;
• Inability to lie flat for the duration of the study;
• Metallic implant or device in the pelvis that might distort the local magnetic field and compromise quality of MRI;
• Any other reason as determined by the investigator or treating physician.
• Patients with an I-PSS score >20 as defined by any pre-treatment IPSS questionnaire.
• Patients with a prior history of transurethral resection of the prostate, TURP, Urolift, or other similar trans-urethral LUTS management procedure within the last 6 months.
• Patients with a prior history of severe urethral stricture.
• Patients with a prior history of pelvic irradiation.
• Patients unable to meet dosimetric constraints
• Patients with a prior history of non-cutaneous solid malignancy within the last 5 years.
• Patients with a history of active and uncontrolled inflammatory bowel disease.
• Patients who are unable to comply with follow-up visits and treatment plans.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Lombardi Comprehensive Cancer Center, Georgetown University — Washington D.C.

Идентификаторы

NCT: NCT07644598 · STUDY00009733

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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