An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care (SoC), Versus SoC Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
PSMAddition
An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
2 other identifiers
interventional
1,145
19 countries
166
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care (SOC), versus Standard of Care alone, in adult male patients with Metastatic hormone sensitive prostate cancer (mHSPC). In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants were enrolled in 20 countries.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2021
Longer than P75 for phase_3
166 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 19, 2021
CompletedFirst Posted
Study publicly available on registry
January 22, 2021
CompletedStudy Start
First participant enrolled
June 9, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 13, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
February 11, 2027
ExpectedMarch 11, 2026
March 1, 2026
3.6 years
January 19, 2021
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Radiographic Progression Free Survival (rPFS)
rPFS is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)
Secondary Outcomes (16)
Overall Survival (OS) (Key Secondary Endpoint)
From date of randomization until date of death from any cause, assessed up to 50 months (estimated final OS analysis)
Prostate-specific antigen 90 (PSA90) response
From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
time to development of mCRPC
From date of randomization till End Of Treatment (EOT) or death, which ever happen first, assessed up to 50 months (estimated final OS analysis)
Progression Free Survival (PFS)
From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)
second Progression Free Survival (PFS2)
From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)
- +11 more secondary outcomes
Study Arms (2)
177Lu-PSMA-617
EXPERIMENTALParticipant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); Androgen receptor-directed therapy (ARDT) + Androgen deprivation therapy (ADT) is considered as SOC and treatment will be administered per the physician's order
Standard of Care
ACTIVE COMPARATORFor participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order
Interventions
Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD
Administered orally on a continuous basis as per package insert and guideline
administered intravenously once every 6 weeks (1 cycle) for 6 cycles
Eligibility Criteria
You may qualify if:
- Signed informed consent must be obtained prior to participation in the study
- Patients must be adults ≥18 years of age
- Patients must have an ECOG performance status of 0 to 2
- Patients must have a life expectancy \>9 months as determined by the study investigator
- Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
- Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
- Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
- Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
- Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
- Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
- Patients must have adequate organ function:
- Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
- Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
- Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
- Albumin ≥2.5 g/dL
- +6 more criteria
You may not qualify if:
- Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
- Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
- Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
- Ongoing participation in any other clinical trial
- Use of other investigational drugs within 30 days prior to day of randomization
- Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
- Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
- Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
- Active clinically significant cardiac disease defined as any of the following:
- NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF \> 45% with improvement in symptoms to class \< 3.
- History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- History of familial long QT syndrome or known family history of Torsades de Pointes
- Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
- History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartis Pharmaceuticalslead
- Alliance Foundation Trials, LLC.collaborator
- RTOG Foundation, Inc.collaborator
Study Sites (166)
Mayo Clinic - Arizona Mayo Clinic Hospital
Scottsdale, Arizona, 85259, United States
Mayo Clinic Arizona
Scottsdale, Arizona, 85259, United States
University of California San Diego - Moores Cancer Center
La Jolla, California, 92093-0658, United States
VA Greater LA Healthcare System
Los Angeles, California, 90073, United States
University of California LA
Los Angeles, California, 90095, United States
St. Joseph Hospital
Orange, California, 92686, United States
Univ Cali Irvine ALS Neuromuscular
Orange, California, 92868, United States
VA Palo Alto Health Care System
Palo Alto, California, 94304-1207, United States
Stanford University Medical Center
Palo Alto, California, 94304, United States
Sansum Clinic
Santa Barbara, California, 93105, United States
Providence Saint Johns Health Ctr
Santa Monica, California, 90404, United States
Univ Of Color Anschutz Med Center
Aurora, Colorado, 80045, United States
Rocky Mountain Cancer Centers
Denver, Colorado, 80218, United States
Hartford Hospital
Hartford, Connecticut, 06102, United States
Georgetown University-Lombardi Cancer Center
Washington D.C., District of Columbia, 20007, United States
VA Medical Center
Washington D.C., District of Columbia, 20422, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Cancer Specialists of North Florida
Jacksonville, Florida, 32256, United States
University Of Miami
Miami, Florida, 33136, United States
Miami Cancer Institute at Bapt
Miami, Florida, 33173, United States
Florida Cancer Affiliates
Panama City, Florida, 32405, United States
University Cancer and Blood Center LLC
Athens, Georgia, 30607, United States
The Queens Medical Centre
Honolulu, Hawaii, 96813, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Hines VA Hospital
Hines, Illinois, 60141, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Tulane Cancer Center
New Orleans, Louisiana, 70112, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Sidney Kimmel CCC At JH
Baltimore, Maryland, 21231, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Uni Of Michigan Health System
Ann Arbor, Michigan, 48109, United States
Corewell Health William Beaum Hosp
Royal Oak, Michigan, 48073-6769, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Mississippi Med Ctr
Jackson, Mississippi, 39216, United States
St. Louis University
St Louis, Missouri, 63104, United States
VA St Louis Health Care System
St Louis, Missouri, 63106, United States
Wash U School of Medicine
St Louis, Missouri, 63110, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Urology Cancer Center PC
Omaha, Nebraska, 68130, United States
University of New Mexico
Albuquerque, New Mexico, 87131 0001, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Ctr
New York, New York, 10065, United States
Univ Of Rochester Cancer Ctr
Rochester, New York, 14642, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Duke Univ Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43221, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, 19107, United States
Univ of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572, United States
Dallas VA Medical Center
Dallas, Texas, 75216, United States
Texas Oncology
Dallas, Texas, 75246, United States
Univ of Texas Southwest Med Center
Dallas, Texas, 75390-9034, United States
MD Anderson
Houston, Texas, 77030, United States
UT Health Science Center
Houston, Texas, 77030, United States
UT Health San Antonio Mays Cancer Center
San Antonio, Texas, 78229, United States
University of Virginia Medical Center
Charlottesville, Virginia, 22908, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
Onco Hemato Asso of SW Virginia
Roanoke, Virginia, 24014, United States
Swedish Medical Center
Seattle, Washington, 98122-4379, United States
Medical College Of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Novartis Investigative Site
Innsbruck, Tyrol, 6020, Austria
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Linz, 4020, Austria
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Vienna, 1090, Austria
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Vancouver, British Columbia, V5Z 1M9, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Montreal, Quebec, H2W 1T8, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1R 2J6, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Nanjing, Jiangsu, 210006, China
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Nanjing, Jiangsu, 210029, China
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Xian, Shanxi, 710032, China
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Chengdu, Sichuan, 610041, China
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Beijing, 100036, China
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Guangzhou, 510060, China
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Shanghai, 200025, China
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Shanghai, 200032, China
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Shanghai, 200080, China
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Tianjin, 300308, China
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Olomouc, 779 00, Czechia
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Prague, 150 06, Czechia
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Copenhagen, DK-2100, Denmark
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Bordeaux, 33075, France
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Clermont-Ferrand, 63011, France
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Lyon, 69373, France
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Montpellier, 34298, France
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Nantes, 44093, France
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Paris, 75015, France
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Paris, 75018, France
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Strasbourg, 67000, France
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Vandœuvre-lès-Nancy, 54511, France
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Villejuif, 94800, France
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Würzburg, Bavaria, 97080, Germany
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Cologne, North Rhine-Westphalia, 50937, Germany
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Essen, 45147, Germany
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München, 80377, Germany
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Münster, 48149, Germany
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Rostock, 18057, Germany
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Nagoya, Aichi-ken, 4668560, Japan
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Sapporo, Hokkaido, 0608648, Japan
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Kobe, Hyōgo, 6500047, Japan
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Yokohama, Kanagawa-ku, 236-0004, Japan
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Suita, Osaka, 5650871, Japan
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Kitaadachi-gun, Saitama, 3620806, Japan
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Bunkyo Ku, Tokyo, 1138431, Japan
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Chuo Ku, Tokyo, 1040045, Japan
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Chiba, 260-8717, Japan
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Fukuoka, 811-0213, Japan
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Fukuoka, 812-0033, Japan
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Fukuoka, 8128582, Japan
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Fukushima, 9601295, Japan
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Kumamoto, 860-8556, Japan
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Kyoto, 6068507, Japan
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Okayama, 7008558, Japan
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Yamagata, 990 9585, Japan
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Nijmegen, Gelderland, 6500HB, Netherlands
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Maastricht, Limburg, 6229 HX, Netherlands
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Delft, South Holland, 2625 AD, Netherlands
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Utrecht, 3584 CX, Netherlands
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Gliwice, Silesian Voivodeship, 44-101, Poland
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Krakow, 30-688, Poland
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Warsaw, 02-781, Poland
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Singapore, 119228, Singapore
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Singapore, 168583, Singapore
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Seoul, Korea, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Sabadell, Barcelona, 08208, Spain
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Majadahonda, Madrid, 28222, Spain
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El Palmar, Murcia, 30120, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
Novartis Investigative Site
Madrid, 28046, Spain
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Valencia, 46026, Spain
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Gothenburg, 413 45, Sweden
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Lund, 221 85, Sweden
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Stockholm, 17176, Sweden
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Bern, 3010, Switzerland
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Lausanne, 1011, Switzerland
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Taipei, 10002, Taiwan
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Taoyuan District, 33305, Taiwan
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Sutton, Surrey, SM2 5PT, United Kingdom
Novartis Investigative Site
Belfast, BT9 7AB, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, NW1 2BU, United Kingdom
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London, NW3 2QG, United Kingdom
Novartis Investigative Site
Middlesbrough, TS4 3BW, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 19, 2021
First Posted
January 22, 2021
Study Start
June 9, 2021
Primary Completion
January 13, 2025
Study Completion (Estimated)
February 11, 2027
Last Updated
March 11, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com