Trial Evaluating the Safety and Efficacy Of MR-Linac-Guided Radiotherapy as Salvage Treatment After External Beam Radiotherapy Recurrence (TUMORNATOR II)

Overview

The purpose of this study is to assess the impact of prostate-specific membrane antigen/positron emission tomography (PSMA/PET)-informed magnetic resonance (MR)-guided radiation therapy on serious toxicity outcomes in patients with biopsy-proven locally radiorecurrent prostate cancer. The primary aim is to evaluate the safety of delivering MR-Linac-guided stereotactic body radiotherapy (SBRT) after prior prostate external beam radiotherapy for recurrent disease, and assess urinary toxicity outcomes at 2 years.

Interventions

• Radiation Stereotactic Body Radiation Therapy (SBRT)
  SBRT will be delivered with a prescription dose of 8 Gy x 5 fractions prescribed to the 95% isodose line encompassing the dominant recurrent intraprostatic lesion (DRIL) as seen on MRI and/or PET PSMA imaging plus 4mm (GTV+4mm=CTV\_40). Remainder of the prostate gland minus CTV\_40 (CTV\_25) will be prescribed to 5 Gy x 5 fractions at the 95% isodose line.
• Drug Androgen Deprivation Therapy (ADT)
  ADT would be given 0-1 months prior to planned SBRT to the prostate for total of 4-6 months. ADT will be administered via Leuprolide or Degarelix monthly injections or daily Relugolix pills.

Primary outcome measures

• Late toxicity (after 90 days) radiation-associated genitourinary (GU) and gastrointestinal (GI) events [Time frame: Month 24]

Secondary outcome measures (7)

• Acute toxicity (occurring within 90 days of the treatment) radiation-associated genitourinary (GU) and gastrointestinal (GI) events [Time frame: Month 24]
• Biochemical progression free survival [Time frame: Month 24]
• Distant metastasis-free survival (DMFS) [Time frame: Month 24]
• Radiographic treatment response rate of target intra-prostatic lesion [Time frame: Month 24]
• Expanded Prostate cancer Index Composite (EPIC-26) Short Form score [Time frame: Month 24]
• International prostate symptom score index (IPSS) score [Time frame: Month 24]
• International Index of Erectile Function (IIEF) score [Time frame: Month 24]

Eligibility criteria

Inclusion criteria

• 18 years of age or older male participants
• Biopsy proven intraprostatic prostate cancer after prior definitive external beam radiotherapy (moderate hypofractionation or Stereotactic Body Radiation Therapy (SBRT) acceptable).

a. NOTE: Seminal vesicle involvement allowed

• Pathology confirming recurrent disease must have evidence of viable cancer as indicated with pathology interpretation where a Gleason score can be assigned
• Serum testosterone ≥ 50 ng/dL determined within 2 months prior to enrollment

a. Prior Androgen Deprivation Therapy (ADT) use acceptable if testosterone level >50ng/dL

• At least 4 weeks must have elapsed from major surgery
• Karnofsky Performance Scale (KPS) ≥ 80% or Eastern Cooperative Oncology Group (ECOG) 0-1
• Prostate size as determined on MRI to be < 90 cc.
• International Prostatism Symptom Score (IPSS) ≤ 20
• Patient must be available for follow-up. After 2 years of follow-up, upon completion of post-treatment biopsy, telephone, and chart review-based follow-up will be acceptable for up to 5 years
• Presence of a T2 and/or DWI-visible prostatic lesion on mpMRI

a. NOTE: Lesion visible on MRI required for enrollment but PSMA/PET avid lesion not required

• Satisfy all MRI screening criteria and be willing to fill out the standard MRI screening form

Exclusion criteria

• History of prostate brachytherapy (low dose rate or high dose rate)
• Actively undergoing androgen deprivation therapy and/or anti-androgens at time of enrollment
• CT or MRI or PET scan evidence of extraprostatic disease
• Patients with one or more positive lymph nodes considered suspicious as determined by clinical assessment on MRI or CT or PET scan
• History of another malignancy within the previous 2 years except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, currently in complete remission, or any other cancer that has been in complete remission for at least 3 years
• Patients with Crohn's disease or ulcerative colitis
• MRI ineligibility due to: the presence of a cardiac pacemaker, defibrillator, or other implanted metallic or electronic device which is considered MR unsafe; severe claustrophobia; inability to lie flat for the duration of the study; etc.
• Metallic implant or device in the pelvis that might distort the local magnetic field and compromise quality of mp-MRI
• Lateral pelvic separation greater than 50 cm and/or anterior-posterior separation greater than 35 cm which are incompatible with MRCAT reconstruction
• Contra-indications to receiving gadolinium contrast or PSMA radioligand
• Karnofsky Performance Scale (KPS) < 80 or ECOG 2+
• Grade 3 or higher toxicity experienced after the initial course of External Beam Radiation Therapy (EBRT)
• Disease free interval < 2 years
• Hx of Transurethral Resection Of Prostate (TURP) within the year
• Prior high-intensity focused ultrasound (HIFU) or Cryotherapy
• Prior history of urethral stricture
• Unable to give informed consent
• Unable to complete quality of life questionnaires

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• NYU Langone Health — New York

Identifiers

NCT: NCT07142967 · 24-00856

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗