A phase II, single arm two-phase, clinical study of individually adapted systemic radioligand therapy with 177Lu-PSMA I&T for patients with metastatic, castration-resistant prostate cancer

简要总结

主要结局

次要结局

• Duration of PSA response, defined as the time from the first documented PSA50 response until PSA progression.
• Proportion of patients achieving a PSA decline of ≥50% from baseline (PSA50 response) at any time during treatment.
• Proportion of patients achieving a PSA decline of ≥90% from baseline (PSA90 response) at any time during treatment.
• Maximum percentage decline in PSA from baseline
• Time from baseline to PSA progression
• Molecular Response Rate (MRR): proportion of patients achieving Complete Molecular Response (CMR) or Partial Molecular Response (PMR) on 18F-DCFPyL PSMA PET/CT at Week 12, Week 24, End of Treatment, and End of Study, compared with baseline.
• Objective Response Rate (ORR): proportion of patients achieving Complete Response (CR) or Partial Response (PR) in measurable soft-tissue disease according to RECIST 1.1, assessed by contrast-enhanced CT at each scheduled imaging assessment, End of Treatment, and End of Study, compared with baseline
• Disease Control Rate (DCR): proportion of patients achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to RECIST 1.1.
• Time to Molecular Progression (TTMP): time from treatment initiation to Progressive Molecular Disease (PMD) on 18F-DCFPyL PSMA PET/CT
• Radiographic Progression-Free Survival (rPFS): time from treatment initiation to radiological progression according to PSMA PET/CT, RECIST 1.1, or death from any cause
• Changes in WHO/ECOG performance status before each treatment and at each follow up visit, compared to baseline
• Changes in pain severity on a VAS scale from 1 to 10 before each treatment and at each follow up visit, compared to baseline
• Time to first skeletal event defined as date of enrolment/baseline to date of first symptomatic bone fracture spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, whichever occurs first.
• Quality of life at each follow up visit compared to baseline
• Adverse events/toxicity at each visit
• Overall survival (OS) after treatment with 177Lu-PSMA I&T
• Evaluate absorbed radiation dose to tumour and normal tissues using SPECT/CT after each treatment with study product
• Experimental EP: Correlations between bPFS and uptake on PSMA-PET/CT and if possible FDG-PET/CT and it’s possible prognostic and predictive value
• Experimental EP: Establishing predictive measures of tumour uptake levels on PET/CT (18F-PSMA and if possible FDG) after first, second and third treatment cycle
• Experimental EP: Correlations between tumour uptake measuses from different modalities; 18F-PSMA-PET/CT (and FDG-PET/CT if possible) uptake rate as well as tumour absorbed radiation dose
• Experimental EP: If possible, correlation between 18F-PSMA-PET/CT and FDG-PET/CT concerning both baseline charachteristics, and patient outcomes
• Experimental EP: Establishing cut-offs of PSMA uptake below or above which 177Lu-PSMA therapy may be less, or more effective, and adapted dosing can be used