eoadjuvant Lu-PSMA radioligand therapy and Ipilimumab in men with very high-risk prostate cancer (NEPI)
- Conditions
- Patients with very high-risk prostate cancer (as defined by a total Gleason-Score =4+4 [ISUP-GG 4+5] and clinical stage cT3 (digital rectal examinations or imaging based) plus clinical nodal status cN+ or Serum-PSA level > 20 ng/ml who are candidates for radical prostatectomy with pelvic lymph node dissection.Therapeutic area: Diseases [C] - Male Urogenital Diseases [C12]
- Registration Number
- CTIS2024-514386-19-00
- Lead Sponsor
- niversitaetsklinikum Essen AöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 58
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 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 oIf TSH is not in normal range, fT3 and fT4 must be determined ofT3 2,3 - 4,5 pg/ml = 3,5 - 7,0 pmol/l ofT4 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)
Distant metastasis (clinical stage M1) on conventional imaging. Oligometastatic 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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The co-primary objectives are to assess feasibility and measures of clinical activity for the rational development of the combination of [177Lu]Lu-PSMA-617 and Ipilimumab as neoadjuvant treatment in localized very high-risk prostate cancer;Secondary Objective: To characterize the safety profile of neoadjuvant treatment with Ipilimumab and [177Lu]Lu-PSMA-617 radioligand therapy before radical prostatectomy according to secondary endpoints;Primary end point(s): Feasibility is defined as the ability to perform prostatectomy on day 85 in at least 75% of the participants of a treatment arm with a maximum delay by 3 weeks., Clinical activity will be measured by pathological complete response (pCR) and minimal residual disease, MRD, defined as a tumor burden of 5 mm or less in greatest dimensions
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0;Secondary end point(s):PSA-progression free survival up to 1 year after prostatectomy