Multicenter, open-label, parallel-group, phase II randomized study in patients with oligometastatic prostate cancer with 1-3 asymptomatic metastases of the soft tissue or bone. Eligible patients will be randomized at 1:1 ratio to Stereotactic Radiotherapy followed by Lu-PSMA (arm A) or Stereotactic Radiotherapy (arm B)
Biochemical recurrence (BCR), i.e. prostate-specific antigen (PSA) only recurrence occurs in nearly one-third of patients, after primary definitive therapy for prostate cancer. PSMA (prostate-specific membrane antigen) is an attractive target for diagnosis and therapy of metastasized prostate cancer (PCa) as its expression levels are directly correlated with androgen independence, metastases and progression. Positron Emission Tomography/Computed Tomography (PET-CT) using PSMA is able to detect \> 50% of relapses with PSA between 0.50 and 1 ng/mL and \>75% with PSA between 1 and 2. Oligometastatic prostate cancer include 1-3 asymptomatic metastatic lesion(s) of the soft tissue or bone. The treatment of oligometastatic disease depends on multiple factors including the site, the size, number and location of metastases, and the effectiveness of treatments. Recent advances in radiation therapy allow to image and treat precisely target lesions within any anatomic region of the body. Stereotactic radiation therapy permit highly conformal and precisely targeted radiation administered in a dose intensive strategy. Local control in excess of 75% has been reported for metastatic prostate cancer with very low toxicity. Lutetium 177-PSMA (177Lu-PSMA) is the most extensively investigated PSMA radioligand for radionuclide therapy in castration resistant prostate cancer (CRPC). Several retrospective studies and three phase II prospective studies demonstrated safety and impressive efficacy of 177Lu-PSMA in metastatic CRPC (mCRPC).The purpose of this study is to evaluate in a randomized phase II study the impact of Lu-PSMA added to stereotactic radiotherapy vs radiotherapy alone in PSMA detected- metastatic lesions of hormone-sensible prostate cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
The radiopharmaceutical 177Lu-PSMA-I\&T will be administered, by slow intravenous injection, in 2 cycles of treatment at 6-8 weekly intervals at a dosage of 7.4 GBq.
Ablative stereotactic radiation on the metastatic sites. Delivered in a 1 to 5 fractions regimen, depending on the target size and the surrounding normal tissue constraints,
UO Medicina Nucleare, AUSL della Romagna
Cesena, FC, Italy
RECRUITINGUO Medicina Nucleare, IRCCS IRST
Meldola, FC, Italy
RECRUITING12-month PSA (Prostate-Specific Antigen)-progression-free survival (PSA-PFS)
To determine the proportion of men with oligometastatic hormone sensitive prostate cancer who have PSA progressed after 12 months from randomization to Stereotactic Radiotherapy and Lu-PSMA versus Radiotherapy alone.
Time frame: 12-months
12-month radiographic Progression-free survival (rPFS), Androgen Deprivation Therapy-Free survival (ADT-FS) and Total progression-free survival (PSA-PFS+rPFS)
To assess radiographic progression free survival (PFS) after 12 months, ADT free survival (ADT-FS) and Total progression-free survival (PSA-PFS+rPFS) of Lu-PSMA + Stereotactic Radiotherapy vs Stereotactic Radiotherapy defined as the time interval between the day of randomization and the day of disease progression.
Time frame: 12-months
Incidence of Treatment-Emergent Adverse Events [Toxicity]
To describe the toxicity of Lu-PSMA + Stereotactic Radiotherapy vs Stereotactic Radiotherapy for the population enrolled using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: 60 months
Overall survival (OS)
To assess overall survival (OS) defined as the time interval between the day of randomization and death or last contact.
Time frame: 60 months
Proportion of subjects with undetectable PSA (<0.2 ng/mL)
To assess proportion of subjects with undetectable PSA (\<0.2 ng/mL) defined as a PSA level ≤0.20 ng/mL as measured during routine follow-up
Time frame: 60 months
Quality of life questionnaire (QLQ)
To assess quality of life in the Lu-PSMA+ Stereotactic Radiotherapy arm vs Stereotactic Radiotherapy only arm using the Functional Assessment of Cancer Therapy - Prostate (FACT-P version 4) questionnaire. The scale ranging from 0-4, where 0 is labeled 'Not at all', and 4 is labeled 'Very Much'.
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NONE
Enrollment
70
Time frame: 60 months