Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer
VISION
VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)
3 other identifiers
interventional
861
10 countries
88
Brief Summary
The primary objective of this study was to compare the two alternate primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) in patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA-617 in addition to best supportive/best standard of care (BSC/BSoC) versus patients treated with best supportive/best standard of care alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 prostate-cancer
Started May 2018
Typical duration for phase_3 prostate-cancer
88 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 13, 2018
CompletedFirst Posted
Study publicly available on registry
April 30, 2018
CompletedStudy Start
First participant enrolled
May 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 27, 2021
CompletedResults Posted
Study results publicly available
May 9, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 14, 2023
CompletedJanuary 13, 2025
December 1, 2024
2.7 years
April 13, 2018
April 12, 2022
December 13, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Radiographic Progression-free Survival (rPFS)
Radiographic progression-free survival (rPFS) was defined as the time (in months) from the date of randomization to the date of radiographic disease progression based on the central review assessment per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death due to any cause. Patients who were alive without radiographic progression at the analysis data cut-off were censored for rPFS at the time of their last evaluable radiographic assessment. Date of censoring for rPFS: 1) The censoring date was the date when the last evaluable radiographic assessment (CT/MRI/bone scan) determined a lack of progression; 2) If there were no evaluable assessments, censoring occurred at the date of randomization; 3) Patients who had 2 or more consecutive missed tumor assessments immediately prior to PD or death were censored at the date of the last evaluable tumor assessment prior to those missing tumor assessments.
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Overall Survival (OS)
Overall Survival (OS) was defined as the time (in months) from the date of randomization to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date. The cut-off date was not used for last contact date, unless the patient was seen or contacted on that date. Final OS was analyzed at the time of Primary analysis (Primary Analysis cut-off date = 27-Jan-2021) and an updated descriptive analysis of OS was re-run at the time of final analysis (Final Analysis cut-off date 14-Dec-2023).
From date of randomization until date of death from any cause, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) and up to 66 months (Final Analysis cut-off date = 14-Dec-2023)
Secondary Outcomes (28)
Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE)
From randomization till 30 days safety follow-up, assessed up to 66 months (Final Analysis cut-off date = 14-Dec-2023)
Overall Response Rate (ORR)
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Disease Control Rate (DCR)
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Duration of Response (DOR)
From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Time to First Symptomatic Skeletal Event (SSE)
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021)
- +23 more secondary outcomes
Study Arms (2)
177Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
EXPERIMENTALPatients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used
Best supportive/best standard of care (BS/BSOC) alone
OTHERPatients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Interventions
Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles. After 4 cycles, patients were assessed for (1) evidence of response, (2) residual disease, and (3) tolerance to 177Lu-PSMA-617. If all 3 assessments were met the patient might received an additional 2 cycles of 177Lu-PSMA-617.
Best supportive/best standard of care as defined by the local investigator
Eligibility Criteria
You may qualify if:
- Patients must have the ability to understand and sign an approved informed consent form (ICF).
- Patients must have the ability to understand and comply with all protocol requirements.
- Patients must be \>= 18 years of age.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Patients must have a life expectancy \>6 months.
- Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader.
- Patients must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
- Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone).
- Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, the patient is eligible if: a. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation, intolerance, etc.).
- Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
- Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL.
- Soft-tissue progression defined as an increase \>= 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
- Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016).
- Patients must have \>= 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained =\< 28 days prior to beginning study therapy.
- +15 more criteria
You may not qualify if:
- 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.
- Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 28 days prior to day of randomization.
- Any investigational agents within 28 days prior to day of randomization.
- Known hypersensitivity to the components of the study therapy or its analogs.
- Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
- Patients with a history of Central Nervous System (CNS) metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).
- A superscan as seen in the baseline bone scan.
- Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, 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.
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, superficial bladder cancer.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Endocytelead
Study Sites (88)
HonorHealth Research Institute
Scottsdale, Arizona, 85258, United States
University of Arizona Cancer Center
Tucson, Arizona, 85719-1454, United States
VA Greater Los Angeles Healthcare System
Los Angeles, California, 90073, United States
University of California Los Angeles, Nuclear Medicine
Los Angeles, California, 90095, United States
Stanford Cancer Institute
Palo Alto, California, 94305, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Yale Cancer Center
New Haven, Connecticut, 06520-8028, United States
Washington DC VA Medical Center, Nuclear Medicine Service
Washington D.C., District of Columbia, 20422, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Northwestern University
Chicago, Illinois, 60611, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
Iowa City VA Medical Center
Iowa City, Iowa, 52246, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Tulane Medical Center, Tulane Cancer Center
New Orleans, Louisiana, 70112, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Chesapeake Urology Associates (CUA) P.A.
Towson, Maryland, 21204, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215-5450, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48105, United States
University of Michigan Hospitals
Ann Arbor, Michigan, 48109, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Saint Louis University Hospital
St Louis, Missouri, 63104, United States
VA St. Louis Health Care System - John Cochran
St Louis, Missouri, 63106, United States
Washington University School of Medicine
St Louis, Missouri, 63110-1093, United States
XCancer Omaha / Urology Cancer Center
Omaha, Nebraska, 68130, United States
Comprehensive Cancer Centers of Nevada - Twain Office
Las Vegas, Nevada, 89169, United States
Regional Cancer Care Associates, Central Jersey Division
East Brunswick, New Jersey, 08816, United States
New Mexico Oncology Hematology Consultants Ltd., New Mexico Cancer Center
Albuquerque, New Mexico, 87109, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
New York Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, 10065, United States
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, 27710, United States
Greater Dayton Cancer Center
Kettering, Ohio, 45409, United States
Oregon Health and Science University, Nuclear Medicine
Portland, Oregon, 97239-3098, United States
Pennsylvania Cancer Specialists & Research Institute
Gettysburg, Pennsylvania, 17325, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572, United States
VA North Texas Health Care System, Nuclear Medicine Service
Dallas, Texas, 75216, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Excel Diagnostics & Nuclear Oncology Center
Houston, Texas, 77042, United States
Emily Couric Clinical Cancer Center
Charlottesville, Virginia, 22903, United States
Swedish Cancer Institute Research
Seattle, Washington, 98104, United States
Jules Bordet Institute
Brussels, Belgium
Saint Luc University Hospital
Brussels, Belgium
University Hospitals Leuven, Campus Gasthuisberg, Department of Nuclear Medicine
Leuven, Belgium
BC Cancer - Vancouver
Vancouver, British Columbia, V5Z 4E6, Canada
London Health Sciences Centre, Division of Nuclear Medicine
London, Ontario, N6A 4L6, Canada
Ottawa Hospital, Cancer Center
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Research Institute, Odette Cancer Center
Toronto, Ontario, M4N 3M5, Canada
CHUM - University Hospital of Montreal
Montreal, Quebec, H2X 3E4, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
CHU of Quebec - Laval University
Québec, G1R 2J6, Canada
Aalborg University Hospital, Oncology Department
Aalborg, Denmark
Aarhus University Hospital, Department of Oncology
Aarhus, Denmark
Rigshospitalet - University Hospital Copenhagen, Department of Oncology
Copenhagen, Denmark
Bergonie Institute
Bordeaux, France
Center Jean Perrin
Clermont-Ferrand, France
Leon Berard Center
Lyon, France
Saint-Louis Hospital
Paris, France
Tenon Hospital
Paris, France
Institute Claudius Regaud, Toulouse Cancer Research Center
Toulouse, France
Gustave Roussy Oncology Institute
Villejuif, France
University Hospital Essen, Clinic for Nuclear Medicine
Essen, Germany
Hospital rechts der Isar, Department of Nuclear Medicine
Munich, Germany
University Hospital Muenster, Department of Nuclear Medicine
Münster, Germany
Rostock University Medical Center, Clinic and Polyclinic for Nuclear Medicine
Rostock, Germany
The Netherlands Cancer Institute
Amsterdam, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
Radboud University Medical Center (Radboudumc)
Nijmegen, Netherlands
UMC Utrecht
Utrecht, Netherlands
VA Caribbean Healthcare System
San Juan, 00921, Puerto Rico
Sahlgrenska University Hospital, Department of Oncology
Gothenburg, Sweden
Skane University Hospital - Barngatan, Clinical Trials Unit
Lund, Sweden
Karolinska University Hospital
Stockholm, Sweden
Norrlands University Hospital, Cancer Center
Umeå, Sweden
Uppsala University Hospital, Department of Oncology
Uppsala, Sweden
Bristol Hematology & Oncology Center
Bristol, United Kingdom
Beatson West of Scotland Cancer Center
Glasgow, United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
Guy's Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Institute of Cancer Research
Sutton, United Kingdom
Related Publications (12)
Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.
PMID: 31595044RESULTChi KN, Yip SM, Bauman G, Probst S, Emmenegger U, Kollmannsberger CK, Martineau P, Niazi T, Pouliot F, Rendon R, Hotte SJ, Laidley DT, Saad F. 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice. Curr Oncol. 2024 Mar 7;31(3):1400-1415. doi: 10.3390/curroncol31030106.
PMID: 38534939RESULTFizazi K, Herrmann K, Krause BJ, Rahbar K, Chi KN, Morris MJ, Sartor O, Tagawa ST, Kendi AT, Vogelzang N, Calais J, Nagarajah J, Wei XX, Koshkin VS, Beauregard JM, Chang B, Ghouse R, DeSilvio M, Messmann RA, de Bono J. Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Jun;24(6):597-610. doi: 10.1016/S1470-2045(23)00158-4.
PMID: 37269841RESULTHerrmann K, Rahbar K, Eiber M, Sparks R, Baca N, Krause BJ, Lassmann M, Jentzen W, Tang J, Chicco D, Klein P, Blumenstein L, Basque JR, Kurth J. Renal and Multiorgan Safety of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer in the VISION Dosimetry Substudy. J Nucl Med. 2024 Jan 2;65(1):71-78. doi: 10.2967/jnumed.123.265448.
PMID: 38050121RESULTKuo PH, Yoo DC, Avery R, Seltzer M, Calais J, Nagarajah J, Weber WA, Fendler WP, Hofman MS, Krause BJ, Brackman M, Kpamegan E, Ghebremariam S, Benson T, Catafau AM, Kendi AT. A VISION Substudy of Reader Agreement on 68Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for 177Lu-PSMA-617 Radioligand Therapy. J Nucl Med. 2023 Aug;64(8):1259-1265. doi: 10.2967/jnumed.122.265077. Epub 2023 May 25.
PMID: 37230533RESULTSartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Perez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322. Epub 2021 Jun 23.
PMID: 34161051RESULTArmstrong AJ, Sartor O, de Bono J, Chi K, Fizazi K, Krause BJ, Herrmann K, Rahbar K, Tagawa ST, Saad F, Beer TM, Wu J, Mirante O, Morris MJ. Association of Declining Prostate-specific Antigen Levels with Clinical Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Receiving [177Lu]Lu-PSMA-617 in the Phase 3 VISION Trial. Eur Urol. 2024 Dec;86(6):552-562. doi: 10.1016/j.eururo.2024.08.021. Epub 2024 Sep 5.
PMID: 39242323RESULTChi KN, Armstrong AJ, Krause BJ, Herrmann K, Rahbar K, de Bono JS, Adra N, Garje R, Michalski JM, Kempel MM, Fizazi K, Morris MJ, Sartor O, Brackman M, DeSilvio M, Wilke C, Holder G, Tagawa ST. Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer. Eur Urol. 2024 Apr;85(4):382-391. doi: 10.1016/j.eururo.2023.12.004. Epub 2024 Jan 6.
PMID: 38185538RESULTHerrmann K, Gafita A, de Bono JS, Sartor O, Chi KN, Krause BJ, Rahbar K, Tagawa ST, Czernin J, El-Haddad G, Wong CC, Zhang Z, Wilke C, Mirante O, Morris MJ, Fizazi K. Multivariable models of outcomes with [177Lu]Lu-PSMA-617: analysis of the phase 3 VISION trial. EClinicalMedicine. 2024 Oct 4;77:102862. doi: 10.1016/j.eclinm.2024.102862. eCollection 2024 Nov.
PMID: 39430616RESULTKuo PH, Morris MJ, Hesterman J, Kendi AT, Rahbar K, Wei XX, Fang B, Adra N, Garje R, Michalski JM, Chi K, de Bono J, Fizazi K, Krause B, Sartor O, Tagawa ST, Ghebremariam S, Brackman M, Wong CC, Catafau AM, Benson T, Armstrong AJ, Herrmann K. Quantitative 68Ga-PSMA-11 PET and Clinical Outcomes in Metastatic Castration-resistant Prostate Cancer Following 177Lu-PSMA-617 (VISION Trial). Radiology. 2024 Aug;312(2):e233460. doi: 10.1148/radiol.233460.
PMID: 39162634RESULTMorris MJ, de Bono J, Nagarajah J, Sartor O, Wei XX, Nordquist LT, Koshkin VS, Chi KN, Krause BJ, Herrmann K, Rahbar K, Vickers A, Mirante O, Ghouse R, Fizazi K, Tagawa ST. Correlation analyses of radiographic progression-free survival with clinical and health-related quality of life outcomes in metastatic castration-resistant prostate cancer: Analysis of the phase 3 VISION trial. Cancer. 2024 Oct 15;130(20):3426-3435. doi: 10.1002/cncr.35438. Epub 2024 Jun 21.
PMID: 39031642RESULTSundlov A, Sjogreen-Gleisner K. Peptide Receptor Radionuclide Therapy - Prospects for Personalised Treatment. Clin Oncol (R Coll Radiol). 2021 Feb;33(2):92-97. doi: 10.1016/j.clon.2020.10.020. Epub 2020 Nov 12.
PMID: 33189510DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
April 13, 2018
First Posted
April 30, 2018
Study Start
May 29, 2018
Primary Completion
January 27, 2021
Study Completion
December 14, 2023
Last Updated
January 13, 2025
Results First Posted
May 9, 2022
Record last verified: 2024-12
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