Lutetium-177 (Lu177) Prostate-Specific Antigen (PSMA)-Directed EndoRadiotherapy

PSMA-directed endoRadiothErapy of Castration-reSISTant Prostate Cancer (RESIST-PC). A Phase II Clinical Trial

This was an open-label, multicenter, prospective trial to assess safety and efficacy of 177Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer.

Upon inclusion patients were randomized in a 1:1 ratio into two treatment doses. Radioligand therapy (RLT) were performed by repeated intravenous (i.v.) injection of 6.0 gigabecquerel (GBq) (+/- 10%) or 7.4 GBq (+/- 10%) 177Lu-PSMA-617 every 8+/- 1 weeks until reaching four cycles or threshold maximum dose to the kidneys of 23 Gray (Gy). All doses after labeling were presented in buffered solution for i.v. injection.

In the initial plan for the study design a total of 200 patients with histologically proven prostate cancer and metastatic castration-resistant prostate cancer (mCRPC) were to be enrolled, however due to early stopping of enrollment only 71 patients were enrolled at time of data base lock. Each patient underwent a screening visit within 14 days prior to receiving study drug. Treatment was continued until either of the following conditions applied:

• Prostate-specific antigen (PSA)/radiographic progression at >= 12 weeks
• Completion of four RLT cycles
• 23 Gy kidney dose would be exceeded by the next cycle as estimated by dosimetry
• Patient withdrawal (e.g. appearance of intolerable adverse events).

Inclusion Criteria:

1. Prostate cancer proven by histopathology
2. Unresectable metastases
3. Progressive disease, both docetaxel naive and docetaxel treated.
4. Castration resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
5. Positive 68Ga-PSMA-11 PET/CT (positron emission computed tomography ) or diagnostic 177Lu-PSMA-617 scintigraphy
6. ECOG 0-2
7. Sufficient bone marrow capacity as defined by WBC (white blood cell ) ≥2.500/μl, PLT (platelet) count ≥100.000/μl, Hb≥9.9 g/dl and ANC≥1500 mm3 for the first cycle and WBC≥2.000/ μl,PLT count ≥75.000/μl, Hb≥8.9 g/dl and ANC≥1000 mm3 for the subsequent cycles
8. Signing of the Informed Consent Form
9. Patients enrolling in this trail should have received either Enzalutamide or Abiraterone

Exclusion Criteria:

1. Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm) or other radionuclide therapy.
2. Glomerular Filtration Rate (GFR) <40 ml/min
3. Serum creatinine > 1.5 ULN
4. AST and ALT>5xULN
5. Urinary tract obstruction or marked hydronephrosis
6. Diffuse bone marrow involvement confirmed by super-scans