Clinical trial NCT05204927: 177Lu-PSMA-I&T for Metastatic Castration-Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastasis From Malignant Tumor of Prostate
Keywords: Radioligand Therapy
Prostate Cancer
177Lu-PSMA
PSMA
ECLIPSE
Lead sponsor: Curium US LLC
Sponsor class: INDUSTRY
First posted: 2022-01-24
Enrollment: 439
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Radiographic Progression Free Survival
timeFrame: 34 weeks
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 156 weeks
measure: Second Radiographic Progression Free Survival (rPFS 2)
timeFrame: 156 weeks
measure: Progression Free Survival
timeFrame: 156 weeks
measure: Second Progression-Free Survival
timeFrame: 156 weeks
measure: PSA50 Response Rate
timeFrame: 156 weeks
measure: Time to First Symptomatic Skeletal Event (SSE)
timeFrame: 156 weeks
measure: Time to Soft Tissue Progression (STP)
timeFrame: 156 weeks
measure: Time to Chemotherapy (TTC)
timeFrame: 156 weeks
measure: Quality of Life Questionnaire- EORTC QLQ-C30
timeFrame: 22 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Institute of Urology, PPLC
state: Arizona
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: San Francisco
country: United States
facility: San Francisco VA Health Care System
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Boca Raton
country: United States
facility: GenesisCare USA
state: Florida
city: Miami
country: United States
facility: Biogenix Molecular LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Plantation
country: United States
facility: GenesisCare USA
state: Florida
city: Tampa
country: United States
facility: Florida Urology Partners, LLP
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Gaithersburg
country: United States
facility: Kaiser Permanente Gaithersburg Medical Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: BAMF Health I PC
state: Michigan
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Troy
country: United States
facility: GenesisCare USA
state: Michigan
city: Burnsville
country: United States
facility: M Health Fairview Ridges Cancer Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: SSM Saint Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Center for Clinical Theranostics Research, Washington University
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: XCancer Omaha / Urology Cancer Center
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Gahanna
country: United States
facility: Central Ohio Urology Group
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Portland
country: United States
facility: OHSU - Center for health and healing
state: Oregon
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Brest
country: France
facility: CHU Brest
city: Clermont-Ferrand
country: France
facility: Jean Perrin Comprehensive Cancer Center
city: Marseille
country: France
facility: Institute Paoli-Calmettes
city: Nancy
country: France
facility: Hôpital de Brabois -CHU
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest (ICO) St Herblain
city: Nîmes
country: France
facility: CHU Nimes
city: Strasbourg
country: France
facility: ICANS
city: Toulouse
country: France
facility: InstitutClaudius Regaud-IUCT-O
city: Bologna
country: Italy
facility: University Clinic Bologna
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia (IEO) -IRCCS
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Salamanca
country: Spain
facility: University Hospital of Salamanca
Study officials:
References: