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

NCT ID: NCT05204927

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

439 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-14

Study Completion Date

2029-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Metastasis From Malignant Tumor of Prostate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Participants will be randomized on a 2:1 basis to receive Lu177-PSMA (Investigational Arm) or standard of care hormone therapy (Control Arm). The Control Arm will consist of treatment with either abiraterone with prednisone or enzalutamide depending on the clinical judgement of the investigator. Participants who are randomized to the control arm who demonstrate radiographic progression may be eligible to crossover to receive Lu177-PSMA.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Of Care Hormone Therapy

Abiraterone with Prednisone or Enzalutamide

Group Type ACTIVE_COMPARATOR

Abiraterone with Prednisone or Enzalutamide

Intervention Type DRUG

Hormone Therapy

Investigational Drug

177Lu-PSMA-I\&T

Group Type EXPERIMENTAL

177Lu-PSMA-I&T

Intervention Type DRUG

Radioligand therapy

Interventions

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177Lu-PSMA-I&T

Radioligand therapy

Intervention Type DRUG

Abiraterone with Prednisone or Enzalutamide

Hormone Therapy

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Curium US LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Arizona Institute of Urology, PPLC

Tucson, Arizona, United States

Site Status

Providence Medical Foundation

Fullerton, California, United States

Site Status

Long Beach Memorial Center

Long Beach, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

San Francisco VA Health Care System

San Francisco, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Providence Saint John's Health Center

Santa Monica, California, United States

Site Status

GenesisCare USA

Boca Raton, Florida, United States

Site Status

Biogenix Molecular LLC

Miami, Florida, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

GenesisCare USA

Plantation, Florida, United States

Site Status

Florida Urology Partners, LLP

Tampa, Florida, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

John Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Kaiser Permanente Gaithersburg Medical Center

Gaithersburg, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

BAMF Health I PC

Grand Rapids, Michigan, United States

Site Status

Michigan Institute of Urology

Troy, Michigan, United States

Site Status

GenesisCare USA

Troy, Michigan, United States

Site Status

M Health Fairview Ridges Cancer Clinic

Burnsville, Minnesota, United States

Site Status

SSM Saint Louis University Hospital

St Louis, Missouri, United States

Site Status

Center for Clinical Theranostics Research, Washington University

St Louis, Missouri, United States

Site Status

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Central Ohio Urology Group

Gahanna, Ohio, United States

Site Status

Hightower Clinical

Oklahoma City, Oklahoma, United States

Site Status

OHSU - Center for health and healing

Portland, Oregon, United States

Site Status

VA Portland Health Care System

Portland, Oregon, United States

Site Status

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Site Status

Houston Metro Urology

Houston, Texas, United States

Site Status

Urology San Antonio

San Antonio, Texas, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

CHU Brest

Brest, , France

Site Status

Jean Perrin Comprehensive Cancer Center

Clermont-Ferrand, , France

Site Status

Institute Paoli-Calmettes

Marseille, , France

Site Status

Hôpital de Brabois -CHU

Nancy, , France

Site Status

Institut de Cancérologie de l'Ouest (ICO) St Herblain

Nantes, , France

Site Status

CHU Nimes

Nîmes, , France

Site Status

ICANS

Strasbourg, , France

Site Status

InstitutClaudius Regaud-IUCT-O

Toulouse, , France

Site Status

University Clinic Bologna

Bologna, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Istituto Europeo di Oncologia (IEO) -IRCCS

Milan, , Italy

Site Status

Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

University Hospital of Salamanca

Salamanca, , Spain

Site Status

Countries

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United States France Italy Spain

Other Identifiers

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CURLu177PSM0001

Identifier Type: -

Identifier Source: org_study_id

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