177Lu-PSMA-I&T for Metastatic Castration-Resistant Prostate Cancer

A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of 177Lu-PSMA-I&T Versus Hormone Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer

A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of 177Lu-PSMA-I&T versus Hormone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastasis From Malignant Tumor of Prostate
• Intervention / Treatment: Drug: Abiraterone with Prednisone or Enzalutamide; Drug: 177Lu-PSMA-I&T

Detailed Description

This is a prospective, open-label, multi-center, randomized, Phase 3 study evaluating Lutetium 177Lu-PSMA-I&T as treatment compared to standard of care hormone therapy in men with metastatic Castration-Resistant Prostate Cancer.

The study will include a total of 400 patients with metastatic prostate cancer and documented positive PSMA PET imaging. Patients will be randomized at a ratio of 2:1 to receive either 177Lu-PSMA-I&T or hormone therapy (abiraterone or enzalutamide) respectively. Patients randomized to the investigational product will receive up to 6 treatments every 6 weeks at a dose of 200 mCi (7.4 GBq). All patients will be followed for adverse events and safety labs throughout the course of the study. Progression of disease will be assessed radiographically using Prostate Working Group Criteria 3 (PWGC3) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of conventional imaging as well as PSA levels and symptom recording throughout the course of treatment.

30 patients will participate in a pharmacokinetic and radiation dosimetry sub-study at selected participating clinical sites. Sub-study participants will receive SPECT imaging after each treatment cycle for dosimetry analysis. Sub-study participants will not be randomized.

• Study Type: Interventional
• Enrollment (Actual): 439
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France
    • CHU Brest
  • Clermont-Ferrand, France
    • Jean Perrin Comprehensive Cancer Center
  • Marseille, France
    • Institute Paoli-Calmettes
  • Nancy, France
    • Hôpital de Brabois -CHU
  • Nantes, France
    • Institut de Cancérologie de l'Ouest (ICO) St Herblain
  • Nîmes, France
    • CHU Nîmes
  • Strasbourg, France
    • ICANS
  • Toulouse, France
    • InstitutClaudius Regaud-IUCT-O
• Italy
  • Bologna, Italy
    • University Clinic Bologna
  • Milan, Italy
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milan, Italy
    • Istituto Europeo di Oncologia (IEO) -IRCCS
• Spain
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Universitario HM Sanchinarro
  • Málaga, Spain
    • Hospital Regional Universitario de Málaga
  • Salamanca, Spain
    • University Hospital of Salamanca
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Institute of Urology, PPLC
  • California
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Center
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
    • San Francisco, California, United States, 94121
      • San Francisco VA Health Care System
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Health Center
  • Florida
    • Boca Raton, Florida, United States, 33431
      • GenesisCare USA
    • Miami, Florida, United States, 33165
      • Biogenix Molecular LLC
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
    • Plantation, Florida, United States, 33324
      • GenesisCare USA
    • Tampa, Florida, United States, 33607
      • Florida Urology Partners, LLP
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Hospital
    • Gaithersburg, Maryland, United States, 20879
      • Kaiser Permanente Gaithersburg Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • BAMF Health I PC
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology
    • Troy, Michigan, United States, 48098
      • GenesisCare USA
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • M Health Fairview Ridges Cancer Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • SSM Saint Louis University Hospital
    • Saint Louis, Missouri, United States, 63110
      • Center for Clinical Theranostics Research, Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68130
      • XCancer Omaha / Urology Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08993
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Herbert Irving Pavilion
    • Syracuse, New York, United States, 13210
      • Suny Upstate Medical University
  • Ohio
    • Gahanna, Ohio, United States, 43230
      • Central Ohio Urology Group
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Hightower Clinical
  • Oregon
    • Portland, Oregon, United States, 97239
      • VA Portland Health Care System
    • Portland, Oregon, United States, 97239
      • OHSU - Center for health and healing
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic Urology
  • Texas
    • Houston, Texas, United States, 77027
      • Houston Metro Urology
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male 18 years or older able to understand and provide signed written informed consent.
2. Histologically or pathologically confirmed prostate adenocarcinoma without predominant small cell component.

3. Progressive disease by one or more of the following criteria:

   1. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL.
   2. Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria).

4. Previous treatment with next-generation androgen receptor (AR)-directed therapy (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).

   1. Must have received no more than one previous AR-directed therapy.
   2. Must have been administered ARAT (abiraterone, enzalutamide, darolutamide, or apalutamide) in the castration-sensitive or castration-resistant setting.
   3. Must have progressed while on ARAT.
5. PSMA-PET scan (e.g., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by central reader.
6. Effective castration with serum testosterone level of <50 ng/dL and plan to continue with chronic medical or surgical castration.
7. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
8. Patients with HIV that are healthy and with a low risk of acquired immune deficiency syndrome related outcomes may participate in the trial at the investigators' discretion.
9. Patients with HBV and HCV may also participate if symptoms are sufficiently managed.
10. Life expectancy of at least 6 months as assessed by investigator.
11. Willing to initiate ARAT therapy determined by investigator.
12. For patients who have partners of childbearing potential: The patient and/or partner must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after the last study drug administration.

Exclusion Criteria:

1. Prior treatment with radioligand therapy including other lutetium-labeled compounds.
2. Prior treatment with radium-223 (Xofigo) within the past 12 weeks.
3. Prior chemotherapy treatment for castration-resistant prostate cancer. Prior docetaxel use in the hormone-sensitive setting is permitted, as long as no more than 6 doses were received, the last dose was administered >1 year prior to consent, and disease progression did not occur during docetaxel treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2
5. Patients with known HRR gene-mutation (BRCA 1/2 encompassing both germline and somatic) who have not been previously treated with olaparib or rucaparib.
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.

7. Inadequate organ and bone marrow function as evidenced by:

   1. Hemoglobin < 8 g/dL.
   2. Absolute neutrophil count < 1.5 x 109/L.
   3. Platelet count < 100 x 109/L.
   4. AST/SGOT and/or ALT/SGPT > 3.0 x ULN.
   5. Total bilirubin > 2 x ULN unless patient has known Gilbert's syndrome and then may be 3 x ULN.
   6. Creatinine clearance (CrCl) < 50 mL/min based on the Cockcroft-Gault equation.
   7. Albumin ≤ 2.75 g/dL
8. Patients who undergo a transfusion for the sole purpose of meeting eligibility for this trial will be excluded.
9. Assessment by the Investigator as unable or unwilling to comply with the requirements of the protocol.
10. Use of an investigational therapeutic drug within the last 4 weeks prior to start of study treatment or scheduled to receive one during the study period.
11. Known CNS metastasis unless received therapy, asymptomatic and neurologically stable.
12. Patients receiving zoledronic acid for bone-targeted therapy must be on stable dose for 4 weeks prior to randomization.
13. Major surgery within 30 days of randomization as determined by the Investigator.

14. Patients with active significant cardiac disease defined by any of the following:

    1. New York Heart Association class 3 or 4 congestive heart failure within 6 months of signing the ICF unless treated with improvement.
    2. Current diagnosis of electrocardiogram abnormalities with significant cardiac arrhythmias
    3. History of long QT syndrome or know history of Torsades de Pointe
    4. History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months of ICF signature
15. Participants with symptomatic cord compression or clinical/radiological findings indicating impending spinal cord compression
16. Patients with a superscan seen on baseline bone scan as determined by investigator.
17. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
18. Previous use of G-CSF for persistent neutropenia after standard of care treatment.
19. Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy.
20. Participants with active Covid19. Recovered patients may be included when completely recovered (no symptoms at least 28 days before study medication and a negative Covid test within 72 hours).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Of Care Hormone Therapy; Abiraterone with Prednisone or Enzalutamide	Drug: Abiraterone with Prednisone or Enzalutamide; Hormone Therapy
Experimental: Investigational Drug; 177Lu-PSMA-I&T	Drug: 177Lu-PSMA-I&T; Radioligand therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression Free Survival	Radiographic progression free survival (rPFS), defined as the time from randomization to radiographic progression (using PCWG3 and RECIST 1.1 criteria as assessed by blinded independent central review [BICR]) or death due to any cause.	34 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time (weeks) from randomization to death due to any cause.	156 weeks
Second Radiographic Progression Free Survival (rPFS 2)	Time from randomization to the second radiographic progression or death in participants who crossover.	156 weeks
Progression Free Survival	First occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.	156 weeks
Second Progression-Free Survival	Second occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.	156 weeks
PSA50 Response Rate	Response rate of patients who achieve a reduction of ≥50% in PSA from the baseline PSA assessment.	156 weeks
Time to First Symptomatic Skeletal Event (SSE)	Occurrence of either bone-directed radiotherapy to relieve bone pain, new symptomatic pathologic fractures, spinal cord compression, or tumor-related orthopedic surgery.	156 weeks
Time to Soft Tissue Progression (STP)	Occurrence of radiographic progression in soft tissue.	156 weeks
Time to Chemotherapy (TTC)	Time from randomization to the initiation of chemotherapy or death.	156 weeks
Quality of Life Questionnaire- EORTC QLQ-C30	The Quality of Life (QoL) will be assessed via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). The EORTC QLQ-C30 is a questionnaire of thirty quality of life (QoL) questions developed to assess the QoL of cancer patients. The EORTC QLQ-C30 comprises 30 items, 24 of which are aggregated into nine multi-item scales, which are scored from 0 to 100.	22 weeks

Collaborators and Investigators

• Sponsor: Curium US LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): August 2, 2024
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; PSMA; Radioligand Therapy; 177Lu-PSMA; ECLIPSE
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: CURLu177PSM0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No