An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.
- Registration Number
- NCT05939414
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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 conventional imaging (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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 450
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617) AAA617 All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 4 cycles.
- Primary Outcome Measures
Name Time Method Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) 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 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.
- Secondary Outcome Measures
Name Time Method European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L) From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Overall survival (OS) From date of randomization until date of death from any cause, assessed up to approximately 74 months Overall Survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. OS time for participants who are alive at the end of the study or are lost to follow-up will be censored at the date of last contact.
Key secondary endpoint: Time to Hormonal Therapy (TTHT) From date of randomization until date of Androgen Deprivation Therapy (ADT), assessed up to approximately 74 months Time to Hormonal Therapy (TTHT) is defined as the time from randomization to the time to Androgen Deprivation Therapy (ADT). The type of hormonal therapy will be at the discretion of the Investigator.
Time to next therapy (local or systemic) From date of randomization until initiation of the next line of therapy (local or systemic), assessed up to approximately 74 months Time to next therapy (local or systemic) is defined as the time from randomization to initiation of the next line of therapy (local or systemic). Next-line therapy is defined as the first new (local or systemic) anti-neoplastic therapy initiated after discontinuation of study treatment regardless of end of treatment (EOT) reason.
Investigator assessed Metastasis Free Survival (MFS) 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 Investigator assessed Metastasis Free Survival (MFS) is defined as the time from randomization to the first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., CT/MRI and bone scans) as assessed by Investigator using RECIST 1.1 or death from any cause, whichever occurs first.
Time to First Symptomatic Skeletal Event (TTSE) From date of randomization till end of treatment (EOT) or death, whichever happens first, assessed up to approximately 74 months Time to first symptomatic skeletal event (TTSSE) is defined as date of randomization to the date of first new SSE or death from any cause, whichever occurs first. Symptomatic skeletal events (SSE) will be defined by the occurrence of any of the following (whichever occurs earlier): symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain.
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACTGeneral (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.
Time to prostate specific antigen (PSA) progression (TTPSAP) From date of randomization until date of first PSA progression, assessed up to approximately 74 months Time to prostate specific antigen (PSA) progression (TTPSAP) is defined as time from randomization to first PSA progression 1. First PSA progression 1 is defined as a rising PSA confirmed on repeated measurement at least 3 weeks later, and at least greater than 25% and \>= 2 ng/mL above nadir or baseline, whichever is lower. In the absence of PSA progression, TTPSAP will be censored at the last PSA measurement.
Radiographic Progression Free Survival (rPFS) 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 Radiographic progression free survival (rPFS) is defined as the time from randomization to first documentation of confirmed radiographic progressive disease or death due to any cause (whichever occurs first) by conventional imaging (i.e., CT/MRI and bone scans) using RECIST 1.1. The rPFS will be analyzed based on BIRC and Investigator assessments respectively.
24-month prostate-specific antigen (PSA) progression free survival (PFS) 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 24-month PSA PFS is defined as PSA PFS at 24 months. PSA PFS is defined as the time from date of randomization to the date of first documented PSA progression 2 or death from any cause, whichever occurs first. PSA progression 2 is defined as a PSA concentration above the nadir (or baseline if lower) of \>= 0.5 ng/mL, confirmed by repeated measurement at least 3 weeks later. PSA PFS will be censored if no PSA PFS event is observed before the first to occur analysis cut-off date. The censoring date will be the date of the last adequate tumor assessment prior to cut-off.
Time to symptomatic progression From date of randomization until date of first documented symptomatic progression, assessed up to approximately 74 months Time to symptomatic progression is defined as time from randomization to the date of first documented event for any of the following, whichever occurs first: development of symptomatic skeletal event, escalation in cancer-related pain or worsening of disease-related symptoms leading to the initiation of a new systemic anticancer therapy, development of clinically significant symptoms due to local or regional tumor progression leading to surgery or radiation therapy.
Dose modifications and intensity for AAA617 From date of randomization until end of treatment (EOT), assessed up to approximately 30 months Dose modifications (dose interruptions and reductions) and dose intensity for AAA617 will be assessed and summarized using descriptive statistics.
Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT) Questionnaire From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months The FACT-RNT (Functional Assessment of Cancer Therapy - Radionuclide Therapy) is a Patient Reported Outcomes (PRO) new measure developed using FACIT specific questions (items), selected from FACIT item bank, to assess treatment-related symptoms of special interest associated with radioligand therapies.
The FACT-RNT contains items assessing dry mouth, dry eyes, vomiting, diarrhea, constipation, loss of appetite, fatigue, impact of fatigue, bone pain, and isolation due to illness or treatment. FACT-RNT score range 0 to 60, with higher score indicating better quality of life.Brief Pain Inventory - Short Form (BPI-SF) Questionnaire From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item selfreport questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Trial Locations
- Locations (29)
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Stanford University
🇺🇸Palo Alto, California, United States
UCSF
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Longmont, Colorado, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Woodlands Medical Specialists
🇺🇸Pensacola, Florida, United States
Piedmont Cancer Institute P C
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
The Cancer Institute of Alexian Brothers
🇺🇸Elk Grove, Illinois, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
University of Maryland Medical Ctr
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Kimmel Com Cancer Ctr
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
BAMF Health
🇺🇸Grand Rapids, Michigan, United States
Profound Research LLC
🇺🇸Royal Oak, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
VA St Louis Health Care System
🇺🇸Saint Louis, Missouri, United States
Wash U School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloane Ketterin Cancer Ctr
🇺🇸New York, New York, United States
Dayton Physicians
🇺🇸Kettering, Ohio, United States
Oregon Urology Institute
🇺🇸Springfield, Oregon, United States
Carolina Urologic Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Univ of Texas Southwest Med Center
🇺🇸Dallas, Texas, United States
Rio Grande Urology
🇺🇸El Paso, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Blue Ridge Cancer Center
🇺🇸Wytheville, Virginia, United States
Novartis Investigative Site
🇬🇧Coventry, United Kingdom