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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT05204927
Recruitment Status : Recruiting
First Posted : January 24, 2022
Last Update Posted : April 7, 2023
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Metastasis From Malignant Tumor of Prostate Drug: 177Lu-PSMA-I&T Drug: Abiraterone with Prednisone or Enzalutamide Phase 3

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 4 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 14, 2022
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : June 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Prednisone

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
Drug: 177Lu-PSMA-I&T
Radioligand therapy

Primary Outcome Measures :
  1. Radiographic Progression Free Survival [ Time Frame: 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 :
  1. Overall Survival (OS) [ Time Frame: 156 weeks ]
    Time (weeks) from randomization to death due to any cause.

  2. Second Radiographic Progression Free Survival (rPFS 2) [ Time Frame: 156 weeks ]
    Time from randomization to the second radiographic progression or death in participants who crossover.

  3. Progression Free Survival [ Time Frame: 156 weeks ]
    First occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.

  4. Second Progression-Free Survival [ Time Frame: 156 weeks ]
    Second occurrence of PCWG3 progression, clinical/symptomatic progression and/or pain progression, or death due to any cause.

  5. PSA50 Response Rate [ Time Frame: 156 weeks ]
    Response rate of patients who achieve a reduction of ≥50% in PSA from the baseline PSA assessment.

  6. Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: 156 weeks ]
    Occurrence of either bone-directed radiotherapy to relieve bone pain, new symptomatic pathologic fractures, spinal cord compression, or tumor-related orthopedic surgery.

  7. Time to Soft Tissue Progression (STP) [ Time Frame: 156 weeks ]
    Occurrence of radiographic progression in soft tissue.

  8. Time to Chemotherapy (TTC) [ Time Frame: 156 weeks ]
    Time from randomization to the initiation of chemotherapy or death.

  9. Quality of Life Questionnaire- EORTC QLQ-C30 [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

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 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05204927

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Contact: Darcy Denner 314-506-3512 Eclipse@curiumpharma.com

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Sponsors and Collaborators
Curium US LLC
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Responsible Party: Curium US LLC
ClinicalTrials.gov Identifier: NCT05204927    
Other Study ID Numbers: CURLu177PSM0001
First Posted: January 24, 2022    Key Record Dates
Last Update Posted: April 7, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Curium US LLC:
Radioligand Therapy
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents