Neoadjuvant Lu-PSMA radioligand therapy and Ipilimumab in men with very high-risk prostate cancer (NEPI)

Trial details

Who runs it

Universitaetsklinikum Essen AöR

Trial code

EU 2024-514386-19-00

Record updated

2025. július 22.

Original description

Co-primary endpoints of the study are feasibility and safety.Read full original descriptionShow less

A phase I study of neoadjuvant treatment with 177-Lutetium-PSMA-617 with Ipilimumab in subjects with very high-risk prostate cancer who are candidates for radical prostatectomy (NEPI Trial)

Co-primary endpoints of the study are feasibility and safety.

Inclusion: Must be ≥18 years of age; Sexually active patients must use a condom to prevent them from fathering a child and to prevent delivery of study treatment via seminal fluid to their partner for at least 14 weeks after the last dose of [177Lu]Lu‐PSMA‐617; Tumor tissue of both prostate biopsy and radical prostatectomy specimen available for local histology review and reference pathology by Professor Henning Reis (Department of Pathology, University Hospital Frankfurt); Signed an informed consent form (ICF) indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study; participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol; Histologically confirmed adenocarcinoma of the prostate including following criteria: Very High‐risk defined by a total Gleason‐Score ≥4+4 (ISUP‐GG 4+5) and clinical stage cT3 (digital rectal examination or imaging based) plus clinical nodal status cN+ or Serum‐PSA level >20ng/ml; Exclusion of metastases (M0) on conventional imaging and maximum oligometastatic status (maximum 3 bone lesions) on PSMA PET imaging; Treatment naïve patients; Eastern Cooperative Oncology Group ECOG 0‐1; Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator; Patients must be PSMA Positron Emission Tomography (PET) scan positive with a prostatic SUVmax > 12 (PRIMARY Score: 5) ; Following laboratory criteria must be obtained within 14 days prior to randomization:  Bone Marrow reserve • White blood cells, WBC ≥ 2000/μL • Neutrophils ≥ 1500/μL • Platelets ≥ 100 x103/μL • Hemoglobin ≥ 9.0 g/dL  Hepatic • AST/ALT ≤ 3 x ULN • Total Bilirubin ≤ 1.5 x ULN (except participants with Gilbert Syndrome, who may have total bilirubin < 3.0 mg/dL)  Renal • Serum creatinine ≤ 1.5xULN  Endocrine • TSH 0,4 ‐ 4,0 mU/l = 0,4 ‐ 4,0 μU/ml o If TSH is not in normal range, fT3 and fT4 must be determined o fT3 2,3 ‐ 4,5 pg/ml = 3,5 ‐ 7,0 pmol/l o fT4 0,8 ‐ 1,8 ng/dl = 8 ‐ 18 ng/l = 10 ‐ 23 pmol/l  Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)  Electrolytes: • Potassium: 3.5‐5 mmol/L • Sodium: 135‐145 mmol/L  Pancreatic: • amylase, lipase ≤ 3 x ULN  alkaline phosphatase (range to be assessed in context of oligometastatic disease)  blood sugar < 200 mg/dL (11.1 mmol/L).

Exclusion: Distant metastasis (clinical stage M1) on conventional imaging. Oligometastatic (maximum 3 bone lesions ) patients on exclusively PSMA PET imaging will not be excluded. Patients with PSA values below 20ng/ml and no evidence of nodal disease are excluded; Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy; Lack of availability for clinical follow‐up assessments; Other potential life‐threatening malignancies within the past five years requiring treatment; Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years; Patients with serious intercurrent illness, requiring hospitalization; Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders; Patients carrying organ transplants and/or receiving continuous immunosuppressive medication (other than steroid therapy of up to 10 mg prednisone per day); The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition; Known hypersensitivity reaction to any of the components of study treatment; Known alcohol or drug abuse; Prior treatment with androgen receptor antagonists. Treatment with GnRH analogs prior to ICF signature; Participation in another clinical study and use of any investigational or non‐registered product (drug or vaccine) other than the study treatment within the 30 days before registration; Significant disease or condition which, in the investigator’s opinion, would exclude the patient from the study; Legal incapacity or limited legal capacity; Bilateral orchiectomy; History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer; Use of any investigational agent ≤4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time; Major surgery ≤4 weeks prior to randomization; Prior therapy with CTLA4 antibodies; Previous treatment with any of the following within 6 months of randomization:  Strontium‐89, Samarium‐153, Rhenium‐186, Rhenium‐188, Radium‐223,  Previous PSMA‐targeted radioligand therapy; Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement and / or steroid therapy up to a maximum dose of 10 mg prednisone or equivalent per day).

EU CTIS 2024-514386-19-00