An International, Prospective, Open-label, Multi-center, Randomized Phase III Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) Versus Observation to Delay Castration or Disease Recurrence in Adult Male Patients With Prostate-specific Membrane Antigen (PSMA) Positive Oligometastatic Prostate Cancer (OMPC)
Summary
The purpose of this study is to evaluate the efficacy and safety of lutetium (177Lu) vipivotide tetraxetan (AAA617) in participants with oligometastatic prostate cancer (OMPC) progressing after definitive therapy to their primary tumor. The data generated from this study will provide evidence for the treatment of AAA617 in early-stage prostate cancer patients to control recurrent tumor from progressing to fatal metastatic disease while preserving quality of life by delaying treatment with androgen deprivation therapy (ADT).
Detailed description
All participants will be assessed for eligibility and will undergo baseline disease assessments including a mandatory gallium (68Ga) gozetotide (also known as \[68Ga\]Ga-PSMA-11) or piflufolastat (18F) ( also known as\[18F\]DCFPyL) PET/CT scan and CI (i.e., CT/MRI and bone scans). Piflufolastat (18F) PET/CT scan will be performed in countries where it is approved. Stereotactic Body Radiation Therapy (SBRT) will be administered to all metastatic Prostate Cancer (PC) lesions after randomization and before the start of treatment with AAA617 or observation. * The duration of SBRT procedures is approximately 3 weeks. * For participants randomized to the investigational arm (AAA617), the treatment duration will be up to 4 cycles of AAA617. For participants randomized to the control arm (observation) the treatment duration will end at the last fraction of SBRT administration. * The visit frequency will be every week 1 and 3 of each of the 4 cycles and every 16 weeks thereafter (for both arms) until first event of disease progression (RECIST 1.1) * The study duration is approximately 6.5 years.
Arms & interventions
- DrugAAA617
Stereotactic Body Radiation Therapy (SBRT) followed by AAA617 will be administered once every 6 weeks (1 cycle) for a planned 4 cycles to participants randomized to the Investigational arm
Outcome measures
Primary
Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS)
Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) is defined as the time from randomization to first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) and bone scans) as assessed by BIRC using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who are alive without distant metastasis at the analysis data cut-off or are lost to follow-up at the time of analysis will be censored for MFS at the time of their last adequate radiographic assessment. Clinical deterioration without objective radiographic evidence will not be considered as documented distant metastasis.
Time frame: From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death due to any cause, whichever occurs first, assessed up to approximately 30 months
Secondary
Key secondary endpoint: Time to Hormonal Therapy (TTHT)
Time frame: From date of randomization until date of Androgen Deprivation Therapy (ADT), assessed up to approximately 74 months
Investigator assessed Metastasis Free Survival (MFS)
Time frame: From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 74 months
Time to prostate specific antigen (PSA) progression (TTPSAP)
Time frame: From date of randomization until date of first PSA progression, assessed up to approximately 74 months
Radiographic Progression Free Survival (rPFS)
Time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 74 months
Time to next therapy (local or systemic)
Time frame: From date of randomization until initiation of the next line of therapy (local or systemic), assessed up to approximately 74 months
24-month prostate-specific antigen (PSA) progression free survival (PFS)
Time frame: From date of randomization until date of first documented PSA progression 2 or death from any cause, whichever occurs first, assessed up to approximately 74 months
Time to symptomatic progression
Time frame: From date of randomization until date of first documented symptomatic progression, assessed up to approximately 74 months
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Time frame: From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT) Questionnaire
Time frame: From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Brief Pain Inventory - Short Form (BPI-SF) Questionnaire
Time frame: From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L)
Time frame: From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Time to First Symptomatic Skeletal Event (TTSE)
Time frame: From date of randomization till end of treatment (EOT) or death, whichever happens first, assessed up to approximately 74 months
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Dose modifications and intensity for AAA617
Time frame: From date of randomization until end of treatment (EOT), assessed up to approximately 30 months
Overall survival (OS)
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 74 months
Eligibility criteria
Study locations (41)
Highlands Oncology Group
Fayetteville, Arkansas, 72703
VA Greater LA Healthcare System
Los Angeles, California, 90073
VA Palo Alto Health Care System
Palo Alto, California, 94304-1207
Stanford University
Palo Alto, California, 94304
UCSF
San Francisco, California, 94115
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Cancer Specialists of North Florida
Jacksonville, Florida, 32256
Woodlands Medical Specialists
Pensacola, Florida, 32503
Piedmont Healthcare
Atlanta, Georgia, 30318
University of Chicago
Chicago, Illinois, 60637
The Cancer Institute of Alexian Brothers
Elk Grove, Illinois, 60007
Unity Point Clinic
Des Moines, Iowa, 50323
University of Kansas Hospital
Kansas City, Kansas, 66160
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
East Jefferson Hospital
Metairie, Louisiana, 70006
University of Maryland Medical Ctr
Baltimore, Maryland, 21201
Johns Hopkins Kimmel Com Cancer Ctr
Baltimore, Maryland, 21231
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215
BAMF Health
Grand Rapids, Michigan, 49503
Profound Research LLC
Royal Oak, Michigan, 48073
William Beaumont Hospital
Royal Oak, Michigan, 48073
Mayo Clinic Rochester
Rochester, Minnesota, 55905
St Louis University
St Louis, Missouri, 63104
VA St Louis Health Care System
St Louis, Missouri, 63106
Wash U School of Medicine
St Louis, Missouri, 63110
The Urology Center PC DBA UroHealth Partners
Omaha, Nebraska, 68114
Memorial Sloan Kettering Cancer Ctr
New York, New York, 10065
Associated Med Professionals of NY
Syracuse, New York, 13210
Montefiore Hospital
The Bronx, New York, 10467 2490
East Carolina University
Greenville, North Carolina, 27858
Dayton Physicians
Kettering, Ohio, 45409
Oregon Urology Institute
Springfield, Oregon, 97477
Coastal Cancer Center
Conway, South Carolina, 29526
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Carolina Regional Cancer Center
Myrtle Beach, South Carolina, 29577
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Univ of Texas Southwest Med Center
Dallas, Texas, 75390-9034
Rio Grande Urology
El Paso, Texas, 79912
Virginia Oncology Associates
Norfolk, Virginia, 23502
Blue Ridge Cancer Center
Wytheville, Virginia, 24382