A Phase III, Multicentre, Randomised Controlled Study to Evaluate the Efficacy and Safety of AZD2265 (FPI-2265) ²²⁵Ac-PSMA-I&T Compared With Standard of Care in Patients With PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)
Summary
The intention of the study is to demonstrate superiority of AZD2265 relative to standard of care treatments by assessment of radiographic progression-free survival (rPFS) and overall survival (OS) in participants with mCRPC.
Detailed description
Approximately 670 adult participants with mCRPC will be randomized to receive either AZD2265 or standard of care treatment (investigator's choice of cabazitaxel, ARPI switch, or radium-223). They will receive their assigned treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Tumor evaluation scans will continue after treatment discontinuation until radiographically confirmed progression or death. All patients will be followed for survival until the end of the study. An Independent Data Monitoring Committee (IDMC) composed of independent experts will be convened to monitor the safety and scientific integrity of the study.
Arms & interventions
- DrugAZD2265
IV
- DrugCabazitaxel
IV in combination with oral prednisone/prednisolone
- DrugAbiraterone
Oral in combination with prednisone/prednisolone
- DrugEnzalutamide
Oral
- DrugApalutamide
Oral
- DrugDarolutamide
Oral
- DrugRezvilutamide
Oral
- DrugRadium-223
IV
Outcome measures
Primary
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time from randomisation to radiographic progression, as assessed by the BICR per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or death due to any cause.
Time frame: From randomization until first radiographic progression per RECIST 1.1/PCWG3 by BICR, or death from any cause, whichever occurs first (up to approximately 33 months)
Overall Survival (OS)
OS is defined as the length of time from randomisation until the date of death due to any cause.
Time frame: From randomization until death from any cause (up to approximately 33 months)
Secondary
Progression-Free Survival (PFS)
Time frame: From randomization until first documented progression (radiographic, clinical, or PSA progression) or death in the absence of progression, whichever occurs first (up to approximately 33 months)
Assessment of PSA50 (≥50% prostate-specific antigen reduction)
Time frame: From C1D1, assessed each treatment cycle then every 8 weeks after EOT until BICR-assessed radiographic progression per RECIST 1.1/PCWG3 (up to approximately 33 months)
Assessment of PSA90 (≥90% prostate-specific antigen reduction)
Time frame: From C1D1, assessed each treatment cycle then every 8 weeks after EOT until BICR-assessed radiographic progression per RECIST 1.1/PCWG3 (up to approximately 33 months)
Objective Response Rate (ORR)
Time frame: From baseline; assessed by BICR per RECIST 1.1/PCWG3 every 8 weeks for first 32 weeks, then every 12 weeks until radiographic progression (up to approximately 33 months)
Duration of Response (DoR)
Time frame: From first documented response until progression per RECIST 1.1/PCWG3 by BICR, or death in the absence of progression, whichever occurs first (up to approximately 33 months)
Symptomatic Skeletal Event-Free Survival (SSE-FS)
Time frame: From randomization until first symptomatic skeletal event or death from any cause, whichever occurs first (up to approximately 33 months)
Plasma concentrations of AZD2265
Time frame: Pre-dose and post-dose on Day 1 of Cycles 1 and 2; 3-24 hours post-dose on Cycle 1 Day 1 only (up to approximately 7 weeks)
Eligibility criteria
Study locations (24)
Research Site
Dothan, Alabama, 36303
Research Site
Phoenix, Arizona, 85004
Research Site
Irvine, California, 92618
Research Site
Loma Linda, California, 92354
Research Site
San Francisco, California, 94143
Research Site
Aurora, Colorado, 80045
Research Site
Miami, Florida, 33165
Research Site
O'Fallon, Illinois, 62269
Research Site
Metairie, Louisiana, 70006
Research Site
Detroit, Michigan, 48201
Research Site
Grand Rapids, Michigan, 49503
Research Site
Omaha, Nebraska, 68130
Research Site
Omaha, Nebraska, 68130
Research Site
Albuquerque, New Mexico, 87109
Research Site
New Hyde Park, New York, 11042
Research Site
New York, New York, 10065
Research Site
Cleveland, Ohio, 44195
Research Site
Dayton, Ohio, 45415
Research Site
Portland, Oregon, 97239
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Myrtle Beach, South Carolina, 29572
Research Site
Nashville, Tennessee, 37203
Research Site
Houston, Texas, 77042
Research Site
Salt Lake City, Utah, 84106