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

Phase 3

Active, not recruiting

• Conditions: Metastasis From Malignant Tumor of Prostate
• Interventions: Drug: Abiraterone with Prednisone or Enzalutamide; Drug: 177Lu-PSMA-I&T

• Registration Number: NCT05204927
• Lead Sponsor: Curium US LLC

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-12-01
• Study First Submitted QC: 2022-01-21
• Study First Posted: 2022-01-24
• Study Start: 2022-02-14
• Primary Completion: 2024-08-02
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-29
• Last Update Posted: 2024-10-31
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 439

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Standard Of Care Hormone Therapy	Abiraterone with Prednisone or Enzalutamide	Abiraterone with Prednisone or Enzalutamide
Investigational Drug	177Lu-PSMA-I&T	177Lu-PSMA-I\&T

Primary Outcome Measures

Name	Time	Method
Radiographic Progression Free Survival	34 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	156 weeks	Time (weeks) from randomization to death due to any cause.
Progression Free Survival	156 weeks	First occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.
Second Progression-Free Survival	156 weeks	Second occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.
PSA50 Response Rate	156 weeks	Response rate of patients who achieve a reduction of ≥50% in PSA from the baseline PSA assessment.
Second Radiographic Progression Free Survival (rPFS 2)	156 weeks	Time from randomization to the second radiographic progression or death in participants who crossover.
Time to First Symptomatic Skeletal Event (SSE)	156 weeks	Occurrence of either bone-directed radiotherapy to relieve bone pain, new symptomatic pathologic fractures, spinal cord compression, or tumor-related orthopedic surgery.
Time to Chemotherapy (TTC)	156 weeks	Time from randomization to the initiation of chemotherapy or death.
Quality of Life Questionnaire- EORTC QLQ-C30	22 weeks	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.
Time to Soft Tissue Progression (STP)	156 weeks	Occurrence of radiographic progression in soft tissue.

Trial Locations

Locations (50)

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Hospital Regional Universitario de Malaga; 🇪🇸 Málaga, Spain

San Francisco VA Health Care System; 🇺🇸 San Francisco, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

Hightower Clinical; 🇺🇸 Oklahoma City, Oklahoma, United States

OHSU - Center for health and healing; 🇺🇸 Portland, Oregon, United States

VA Portland Health Care System; 🇺🇸 Portland, Oregon, United States

Urology San Antonio; 🇺🇸 San Antonio, Texas, United States

Arizona Institute of Urology, PPLC; 🇺🇸 Tucson, Arizona, United States

Providence Medical Foundation; 🇺🇸 Fullerton, California, United States

Long Beach Memorial Center; 🇺🇸 Long Beach, California, United States

GenesisCare USA; 🇺🇸 Troy, Michigan, United States

Providence Saint John's Health Center; 🇺🇸 Santa Monica, California, United States

Biogenix Molecular LLC; 🇺🇸 Miami, Florida, United States

John Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

NorthShore University HealthSystem-Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

Kaiser Permanente Gaithersburg Medical Center; 🇺🇸 Gaithersburg, Maryland, United States

BAMF Health I PC; 🇺🇸 Grand Rapids, Michigan, United States

M Health Fairview Ridges Cancer Clinic; 🇺🇸 Burnsville, Minnesota, United States

XCancer Omaha / Urology Cancer Center; 🇺🇸 Omaha, Nebraska, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Columbia University Medical Center - Herbert Irving Pavilion; 🇺🇸 New York, New York, United States

Central Ohio Urology Group; 🇺🇸 Gahanna, Ohio, United States

SUNY Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Houston Metro Urology; 🇺🇸 Houston, Texas, United States

MidLantic Urology; 🇺🇸 Bala-Cynwyd, Pennsylvania, United States

Jean Perrin Comprehensive Cancer Center; 🇫🇷 Clermont-Ferrand, France

CHU Brest; 🇫🇷 Brest, France

Hôpital de Brabois -CHU; 🇫🇷 Nancy, France

Institute Paoli-Calmettes; 🇫🇷 Marseille, France

CHU Nimes; 🇫🇷 Nîmes, France

ICANS; 🇫🇷 Strasbourg, France

InstitutClaudius Regaud-IUCT-O; 🇫🇷 Toulouse, France

University Clinic Bologna; 🇮🇹 Bologna, Italy

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Istituto Europeo di Oncologia (IEO) -IRCCS; 🇮🇹 Milan, Italy

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

University Hospital of Salamanca; 🇪🇸 Salamanca, Spain

Florida Urology Partners, LLP; 🇺🇸 Tampa, Florida, United States

SSM Saint Louis University Hospital; 🇺🇸 Saint Louis, Missouri, United States

Institut de Cancérologie de l'Ouest (ICO) St Herblain; 🇫🇷 Nantes, France

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milan, Italy

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Center for Clinical Theranostics Research, Washington University; 🇺🇸 Saint Louis, Missouri, United States

Michigan Institute of Urology; 🇺🇸 Troy, Michigan, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States