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)


Condition: Prostate Cancer

Intervention:

  • Drug: 177Lu-PSMA-617
  • Other: Best supportive/best standard of care

Purpose: The primary objective of this study is to compare overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/best standard of care versus patients treated with best supportive/best standard of care alone. Key secondary objectives are an arm-to-arm comparison of the following: - Radiographic progression-free survival (rPFS) - Response Evaluation Criteria in Solid Tumors (RECIST) response - Time to a first symptomatic skeletal event (SSE) Additional Secondary Objectives: - Safety and tolerability of 177Lu-PSMA-617 - Health-related quality of life (HRQoL; EQ-5D-5L, FACT-P and Brief Pain Inventory - Short Form (BPI-SF)) - Health economics - Progression-free survival (PFS) (radiographic, clinical, or prostate-specific antigen [PSA] progression-free survival) - Biochemical response as measured by PSA. Alkaline phosphatase [ALP] levels and lactate dehydrogenase [LDH] levels will also be measured.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03511664

Sponsor: Endocyte

Primary Outcome Measures:

  • Measure: Overall Survival
  • Time Frame: Every 6-8 weeks until end of treatment and every 3 months during long term follow up [up to 24 months
  • Safety Issue:

Estimated Enrollment: 750

Study Start Date: May 23, 2018

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • To qualify for enrollment, patients must meet the following criteria: 1. Patients must have the ability to understand and sign an approved ICF. 2. Patients must have the ability to understand and comply with all protocol requirements. 3. Patients must be ≥18 years of age. 4. Patients must have an ECOG performance status of 0 to 2. 5. Patients must have a life expectancy >6 months. 6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer. 7. Patients must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the sponsor's central reader. 8. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L). 9. Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone). 10. 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: 1. The patient is not willing to receive a second taxane regimen, or 2. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation or intolerance). 11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum 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. 2. 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. 3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016). 12. 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. 13. Patients must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.). 14. Patients must have adequate organ function: 1. Bone marrow reserve:
  • White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 10^9/L is equivalent to 2.5 x 10^3/µL and 2.5 x K/µL and 2.5 x 10^3/cumm and 2500/µL) OR absolute neutrophil count (ANC) ≥1.5 x 10^9/L (1.5 x 10^9/L is equivalent to 1.5 x 10^3/µL and 1.5 x K/µL and 1.5 x 10^3/cumm and 1500/µL)
  • Platelets≥ 100 x 10^9/L (100 x 10^9/L is equivalent to 100 x 10^3/µL and 100 x K/µL and 100 x 10^3/cumm and 100,000/µL)
  • Hemoglobin≥ 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L) 2. Hepatic:
  • Total bilirubin ≤1.5 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 3. Renal:
  • Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min 15. Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L) 16. Patients on a stable bisphosphonate or denosumab regimen for ≥30 days prior to randomization are eligible. 17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. For patients who have partners of childbearing potential: 18. Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principle investigator during the study and for 3 months after last study drug administration.

Exclusion Criteria:

  • Patients who meet any of the following criteria will be excluded from the study: 1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization. Previous PSMA-targeted radioligand therapy is not allowed. 2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomization. 3. Any investigational agents within 28 days prior to day of randomization. 4. Known hypersensitivity to the components of the study therapy or its analogs. 5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy. 6. Transfusion within 30 days of randomization. 7. Patients with a history of 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). 8. A superscan as seen in the baseline bone scan. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 10. 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, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. 11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, superficial bladder cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.

Contact:

  • Richard Messmann, MD
  • 765-476-1070

Locations:

  • HonorHealth 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
  • UCLA
  • Los Angeles California 90095-7370 United States
  • Stanford University
  • Palo Alto California 94304 United States
  • UCSF Medical Center at Mission Bay
  • San Francisco California 94158 United States
  • University of Colorado Denver
  • Aurora Colorado 80045 United States
  • Yale Cancer Center, Clinical Trials Office
  • New Haven Connecticut 06519 United States
  • Washington DC VA Medical Center, Nuclear Medicine Service
  • Washington 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 Cancer Institute
  • Fort Wayne Indiana 46845 United States
  • IU Melvin and Bren Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • University of Iowa Hospitals and Clinics Cancer Center Research
  • Iowa City Iowa 52242 United States
  • Iowa VA Medical Center
  • Iowa City Iowa 52246 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40207 United States
  • Tulane Cancer Center
  • New Orleans Louisiana 70112 United States
  • University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
  • Baltimore Maryland 21201 United States
  • Chesapeake Urology Research Associates
  • Towson Maryland 21204 United States
  • Beth Israel Deaconess Medical Center
  • Boston Massachusetts 02215 United States
  • The Lank Center for Genitourinary Oncology
  • Boston Massachusetts 02215 United States
  • VA Ann Arbor Healthcare System
  • Ann Arbor Michigan 48105 United States
  • University of Michigan Medical Center, Division of Nuclear Medicine
  • Ann Arbor Michigan 48109 United States
  • Karmanos Cancer Center
  • Detroit Michigan 48201 United States
  • Mayo Clinic
  • Rochester Minnesota 55905 United States
  • John Cochran St. Louis Veterans Medical Center
  • Saint Louis Missouri 63106 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110-1093 United States
  • St. Louis University Hospital
  • Saint Louis Missouri 63110 United States
  • GU Research Network/ Urology Cancer Center
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89148 United States
  • Regional Cancer Care Associates
  • East Brunswick New Jersey 08816 United States
  • New Mexico Oncology & Hematology Consultants
  • 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 School of Medicine, Duke Cancer Institute
  • Durham North Carolina 27710 United States
  • Precision Cancer Research/ Dayton Physicians Network
  • Kettering Ohio 45409 United States
  • Oregon Health and Science University Nuclear Medicine Department
  • Portland Oregon 97239-3098 United States
  • Gettysburg Cancer Center
  • 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
  • Dallas VA Research Organization
  • Dallas Texas 75216 United States
  • UT Southwestern Medical Center
  • Dallas Texas 75390 United States
  • Excel Diagnostics & Nuclear Oncology Center
  • Houston Texas 77042 United States
  • UVA Cancer Care
  • Charlottesville Virginia 22903 United States
  • Swedish Cancer Institute
  • Seattle Washington 98104 United States
  • Cliniques Universitaires Saint Luc
  • Brussels Belgium
  • Institut Jules Bordet
  • Brussels Belgium
  • University Hospitals Leuven, Campus Gasthuisberg, Department of Nuclear Medicine
  • Leuven 3000 Belgium
  • BC Cancer - Vancouver
  • Vancouver British Columbia V5Z 4E6 Canada
  • London Health Sciences Centre, Division of Nuclear Medicine
  • London Ontario N6A 5W9 Canada
  • The Ottawa Hospital Cancer Centre
  • Ottawa Ontario K1H8L6 Canada
  • Odette Cancer Centre
  • Toronto Ontario M4N 3M5 Canada
  • CHUM - Hotel Dieu Hospital
  • Montréal Quebec H2X OA9 Canada
  • Jewish General Hospital
  • Montréal Quebec H3T 1E2 Canada
  • Hotel Dieu Hospital in Quebec
  • Québec Quebec G1R2J6 Canada
  • Aalborg University Hospital Klinik Kirurgi-Kræft Clinical Research Unit Department of Oncology
  • Aalborg Denmark
  • Aarhus Universitetshospital
  • Aarhus Denmark
  • Rigshospitalet - University Hospital Copenhagen, Department of Oncology
  • Copenhagen Denmark
  • Bergonie Institute
  • Bordeaux 33076 France
  • Center Jean Perrin
  • Clermont-Ferrand France
  • Leon Berard Center
  • Lyon France
  • Centre d'Investigations et de Recherche Clinique en Oncologie Hospital SAINT-LOUIS
  • Paris France
  • Tenon Hospital
  • Paris France
  • Institute Claudius Regaud, Toulouse Cancer Research Center
  • Toulouse France
  • Gustave Roussy Oncology Institute
  • Villejuif France
  • The Netherlands Cancer Institute
  • Amsterdam 1066 Netherlands
  • St. Antonius Hospital
  • Nieuwegein Netherlands
  • Radboud University Medical Center
  • Nijmegen 6525 GA Netherlands
  • Universitair Medisch Centrum Utrecht
  • Utrecht Netherlands
  • VA Caribbean Healthcare System
  • San Juan 00921 Puerto Rico
  • Sahlgrenska University Hospital, Department of Oncology
  • Gothenburg Sweden
  • Skane University Hospital
  • Lund Sweden
  • Karolinska University Hospital
  • Stockholm SE 17176 Sweden
  • Norrlands Universitetssjukhus
  • Umeå Sweden
  • Uppsala University Hospital, Department of Oncology
  • Uppsala Sweden
  • Institute of Cancer Research
  • Sutton Surrey SM2 5NG United Kingdom
  • Bristol Hematology & Oncology Center
  • Bristol BS2 8ED United Kingdom
  • Beatson West of Scotland Cancer Center
  • Glasgow G12 OYN United Kingdom
  • Royal Surrey County Hospital NHS Foundation Trust
  • Guildford United Kingdom
  • University College London Hospitals NHS Foundation Trust
  • London NW1 2PG United Kingdom
  • Royal Free London NHS Foundation Trust Royal Free Hospital
  • London NW3 2QG United Kingdom
  • Guy's Hospital
  • London United Kingdom
  • St Bartholomew's Hospital, West Smithfield
  • London United Kingdom
  • University Hospital Southampton NHS Foundation Trust
  • Southampton SO16 6YD United Kingdom

View trial on ClinicalTrials.gov


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