- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06388369
Neoadjuvant Lu-PSMA Radioligand Therapy and Ipilimumab in Men With Very High-risk Prostate Cancer (NEPI)
A Randomized Phase I/II Study of Neoadjuvant Treatment With 177-Lutetium- PSMA-617 With or Without Ipilimumab in Subjects With Very High-risk Prostate Cancer Who Are Candidates for Radical Prostatectomy (NEPI Trial)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A randomized, open-label Phase I/II study of neoadjuvant treatment with [177Lu]Lu-PSMA-617 radioligandtherapy (LuPSMA) with or without Ipilimumab in participants with very high-risk prostate cancer who are candidates for Radical Prostatectomy.
The study will be initiated by a safety cohort regarding the [177Lu]Lu- PSMA-617 dose including 6 to 12 patients, who will receive combination therapy with [177Lu]Lu-PSMA-617 and Ipilimumab. The Safety-Run-In-Phase follows a "none of three or one of six patients experienced intolerable events" approach per dose level. That is: The first 3 patients will receive 4 courses of ipilimumab (3 mg/kg) and 2 courses of 3.7 GBq [177Lu]Lu-PSMA-617. If no more than one of these patients develop grade 4 adverse reactions (ARs) without recovery within 3 weeks, another 3 patients will receive the same dosage. If no grade 4 AEs are observed in this second set of patients, we will enroll an additional 3 patients to increase the [177Lu]LuPSMA 617 dose to 7.4 GBq. If no more than one of those patients develop grade 4 ARs without recovery within 3 weeks back to grade ≤1 or to baseline values, another 3 patients will receive the same increased dosage. Provided that these patients do not develop grade 4 ARs, randomization of patients will be started. If the "none of three or one of six patients experienced intolerable events" approach per dose level is not passed the study will be terminated at this point.
46 patients with newly diagnosed very high-risk prostate cancer will be randomly assigned in a 1:1 ratio (Ipilimumab + [177Lu]Lu-PSMA- 617 vs. [177Lu]Lu-PSMA-617 alone) to receive 2 cycles of 7,4 GBq [177Lu]Lu-PSMA-617 with or without 4 cycles of concomitant Ipilimumab 3mg/kg prior to prostatectomy. Radioligandtherapy will be given at 6 weeks intervals while ipilimumab will be given every 3 weeks. For application of ipilimumab and [177Lu]Lu-PSMA-617 within one cycle (week 1 and 7), [177Lu]Lu-PSMA-617 is administered on day 1 and ipilimumab on day 3. ADT will be applied to all patients during the neoadjuvant treatment phase.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: PD Dr. med. Ulrich Krafft
- Phone Number: +49 (0) 201 723 3211
- Email: ulrich.krafft@uk-essen.de
Study Contact Backup
- Name: Nina Nacke
- Email: nina.nacke@uk-essen.de
Study Locations
-
-
-
Essen, Germany, 45147
- University Hospital Essen, Clinic of Urology
-
Contact:
- PD Dr. med. Ulrich Krafft
- Email: ulrich.krafft@uk-essen.de
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must be ≥18 years of age
- 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
- If TSH is not in normal range, fT3 and fT4must be determined fT3 2,3 - 4,5 pg/ml = 3,5 -7,0 pmol/l 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)
- 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).
Exclusion Criteria:
- 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.
- Prior treatment with androgen receptor antagonists. Treatment with GnRH analogs prior to ICF signature
- 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)
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Neoadjuvant Combination Therapy
4 cycles of Ipilimumab 3mg/kg + 2 cycles of 7,4 GBq [177Lu]Lu-PSMA-617
|
2 cycles of 7,4 GBq [177Lu]Lu-PSMA-617 at 6 weeks intervals
4 cycles of Ipilimumab 3mg/kg at 3 weeks intervals
|
Active Comparator: Neoadjuvant Mono Therapy
2 cycles of 7,4 GBq [177Lu]Lu-PSMA-617
|
2 cycles of 7,4 GBq [177Lu]Lu-PSMA-617 at 6 weeks intervals
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility to perform prostatectomy on time
Time Frame: During the intervention/procedure
|
Feasibility will be defined as the ability to perform prostatectomy in at least 75% of the Analysis population 85 days after start of neoadjuvant treatment with a maximum delay by 3 weeks.
A treatment arm will be deemed not feasible in the actual study if >25% of patients of that arm required a delay of surgery >3 weeks.
|
During the intervention/procedure
|
Clinical activity: Proportion of participants in the full analysis set who achieve a pCR
Time Frame: After surgery
|
The proportion of participants in the full analysis set who achieve a pathological complete response (pCR).
The assessment of pCR will be reviewed by the central pathologist for all randomized patients with Radical Prostatectomy with pelvic lymphadenectomy conducted.
The proportion of participants in the full analysis set who achieve a MRD.
The assessment of MRD will be reviewed by the central pathologist for all randomized patients with Radical Prostatectomy with pelvic lymphadenectomy conducted.
|
After surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety Profile of neoadjuvant treatment before radical prostatectomy
Time Frame: Start of neoadjuvant treatment up to 1 year after surgery
|
Characterizing the safety profile of neoadjuvant treatment with Ipilimumab and [177Lu]Lu-PSMA-617 RLT before radical prostatectomy according to AEs and SAEs measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
|
Start of neoadjuvant treatment up to 1 year after surgery
|
Safety Profile of neoadjuvant treatment before radical prostatectomy
Time Frame: Start of neoadjuvant treatment up to 1 year after surgery
|
Measures of PSA progression-free survival for up to 1 year after prostatectomy.
|
Start of neoadjuvant treatment up to 1 year after surgery
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- CA184-608
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Very High Risk Prostate Carcinoma
-
Array BioPharmaCompletedAML | Advanced and Selected Solid Tumors | High Risk and Very High Risk MDSUnited States, Australia, Italy, Spain, France, Switzerland, United Kingdom
-
AstraZenecaCompletedPostoperative or Postradiation Adjuvant Androgen Deprivation Therapy in Locally Advanced Prostate Cancer (High and Very High Risk) PatientsRussian Federation
-
Cancer Trials IrelandJanssen, LPCompleted
-
Azienda Socio Sanitaria Territoriale degli Spedali...TakedaUnknownIntermediate Risk Prostate Cancer | High Risk Prostate CancerItaly
-
Haaglanden Medical CentreTata Memorial CentreNot yet recruitingHigh Risk Prostate CarcinomaNetherlands
-
FutureChemRecruitingHigh Risk Prostate CarcinomaKorea, Republic of
-
Dana-Farber Cancer InstituteMedivation, Inc.CompletedProstate Cancer | Prostate Adenocarcinoma | High Risk Prostate CancerUnited States
-
Schrödinger, Inc.RecruitingAcute Myeloid Leukemia | High-Risk and Very High-Risk Myelodysplastic SyndromesUnited States
-
Ivan de Kouchkovsky, MDNot yet recruitingProstate Cancer | High Risk Prostate CarcinomaUnited States
-
Xijing HospitalRecruitingHigh-Risk Percutaneous Coronary Intervention (High-risk PCI) | Left Ventricular Assist DevicesChina
Clinical Trials on [177Lu]Lu-PSMA-617
-
Peter MacCallum Cancer Centre, AustraliaEndocyte; Movember Foundation; Medical Research Future Fund; E.J. Whitten Foundation...Active, not recruitingProstatic NeoplasmsAustralia
-
Vadim S KoshkinEli Lilly and Company; Prostate Cancer FoundationActive, not recruitingCastration-Resistant Prostate Carcinoma | Stage IV Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8 | Metastatic Castration-resistant Prostate Cancer | Metastatic Prostate Adenocarcinoma | Metastatic Castration-resistant Prostate CarcinomaUnited States
-
Novartis PharmaceuticalsRecruitingProstate CancerUnited States
-
Australian and New Zealand Urogenital and Prostate...Astellas Pharma Inc; Endocyte; Prostate Cancer Research Alliance; National Health...Active, not recruitingMetastatic Castration-Resistant Prostate CancerAustralia
-
Peking Union Medical College HospitalNational Institute for Biomedical Imaging and Bioengineering (NIBIB)RecruitingMetastatic Castration-resistant Prostate CancerChina
-
Radboud University Medical CenterCompleted
-
Centre Georges Francois LeclercNot yet recruitingPatients With Metastatic Castration-resistant Prostate Cancer
-
Novartis PharmaceuticalsRecruitingMetastatic Castration-Resistant Prostate Cancer (mCRPC)Spain, France
-
University of California, San FranciscoNational Cancer Institute (NCI); Prostate Cancer FoundationActive, not recruitingCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Prostate Adenocarcinoma | Stage IV Prostate Cancer | Castration Levels of Testosterone | Stage IVA Prostate Cancer | Stage IVB Prostate CancerUnited States
-
Medical University of ViennaRecruiting