An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexMale
Age18-100
SponsorNovartis Pharmaceuticals
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed prostate cancer prior to randomization
Participants must have biochemically recurrent disease after definitive treatment to prostate by Radical Prostatectomy ((RP), (alone or with post-operative radiation to prostate bed/pelvic nodes)) or External beam Radiation Therapy (EBRT), (prostate alone or prostate with seminal vesicle and/or pelvic nodes) and/or brachytherapy prior to randomization. Biochemical recurrence (BCR) is defined as: nadir PSA + 2 ng/mL post XRT (if participant received-radiation therapy to intact prostate) and PSA > 0.2 ng/mL and rising post RP (with or without post-operation Radiation Therapy (RT))
Participants must have OMPC with 1-5 PSMA -positive metastatic lesions on screening PSMA PET/CT scan (with either gallium (68Ga) gozetotide or piflufolastat (18F)) as visually assessed by BIRC. For definition of PSMA PET positivity, please refer to Section 8.1 and the Imaging Manual. Metastatic lesions may include regional/pelvic lymph nodes (N1), distant lymph nodes (M1a), bone (M1b), lung and others visceral (M1c) except liver and brain classified using American Joint Committee on Cancer (AJCC) 8. When counting the number of oligometastatic lesions, each lesion is counted as distinct metastasis irrespective of its anatomical location (e.g., one pelvic and one extra-pelvic lymph node will be counted as two metastatic lesions)
At least 1 PSMA-positive lesion must be a distant metastasis (M1) per AJCC8 classification at screening. For AJCC M staging, PSMA PET/CT information should be used
Disqualifiers
Participants with de novo OMPC at screening
Unmanageable concurrent bladder outflow obstruction or urinary incontinence at screening. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed
ADT (including bilateral orchiectomy) and ARPIs used for metastatic prostate cancer treatment
Participants who received AR-directed therapy, whether ADT or an ARPI or both, as neoadjuvant or adjuvant therapy as a component of their primary therapy, are eligible provided that they discontinued therapy ≥12 months prior to randomization for ADT (i.e., 12 months after the last day of the last injection) or ≥3 months if ARPI was given as monotherapy. ARPI's as a term includes both contemporary androgen synthesis inhibitors (e.g., abiraterone, galeterone, and orteneronel), and receptor inhibitors (enzalutamide, apalutamide and darolutamide).
Trial design
Design model
Parallel
Treatments tested in this trial
AAA617
DrugRadiopharmaceutical solution for infusion/injection
piflufolastat (18F)
DrugProvided as ready-to-use radiopharmaceutical
gallium (68Ga) gozetotide (25μg)
DrugProvided as PSMA-11 Kit for radiopharmaceutical preparation of gallium (68Ga) gozetotide
Treatment groups
450 Participants
are divided into 2 treatment groupsGroup A: Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617)Experimental treatment 3 interventions
Group B: Control arm: observation (watchful waiting)No intervention 0 interventions
Trial outcomes
Primary outcomes
1
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 monthsSecondary outcomes
1
Key secondary endpoint: Time to Hormonal Therapy (TTHT)
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 frame
From date of randomization until date of Androgen Deprivation Therapy (ADT), assessed up to approximately 74 months2
Investigator assessed Metastasis Free Survival (MFS)
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 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 months3
Time to prostate specific antigen (PSA) progression (TTPSAP)
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.
Time frame
From date of randomization until date of first PSA progression, assessed up to approximately 74 months4
Radiographic Progression Free Survival (rPFS)
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.
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 monthsSponsors and contacts
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Source ClinicalTrials.gov