Clinical trial NCT05849298: A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC
Official title: An International Prospective Open-label, Multi-center, Randomized, Non-comparative Phase II Study of Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) Alone and Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) in Combination With Androgen Receptor Pathway Inhibitors in Patients With PSMA PET Scan Positive Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostatic Neoplasm
Keywords: Prostate-specific membrane antigen (PSMA)
Lutetium [177Lu] vipivotide tetraxetan (AAA617)
Androgen Receptor Pathway Inhibitors (ARPI)
Enzalutamide
Darolutamide
Apalutamide
Castration Resistant Prostate Cancer
Androgen Deprivation Therapy
gallium [68Ga] gozetotide (AAA517)
piflufolastat F 18
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-05-08
Enrollment: 120
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: No cross-over allowed
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of AAA617 alone (Lutetium \[177Lu\] vipivotide tetraxetan) and in combination with an Androgen Receptor Pathway Inhibitors (ARPI) in participants with PSMA-positive, castration-resistant prostate cancer and no evidence of metastasis in conventional imaging (CI) (i.e., CT/MRI and bone scans). Approximately 120 participants will be randomized.


Eligibility criteria: Key Inclusion criteria

* Participants must be adults ≥ 18 years of age with signed informed consent prior to participation to study
* Histologically or cytologically confirmed prostate cancer
* Participants must have ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy
* Castrate level of serum testosterone (\< 1.7 nmol/l \[50 ng/dl\]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy
* Participants must have evidence of PSMA-positive disease as seen on a AAA517 or piflufolastat F 18 PET/CT scan at baseline as determined by Blinded Independent Central Review (BICR) based on the methodology proposed in the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) (Eiber et al 2018). Participants with M1 disease only on PSMA PET scan are allowed to participate
* Participants must have a negative conventional imaging for M1 disease.
* PSA Doubling Time (PSADT) of ≤ 10 months
* Participants must have adequate organ functions: bone marrow reserve, hepatic \& renal

Key Exclusion criteria

* Prior or present evidence of metastatic disease as assessed by CT/MRI locally for soft tissue disease and whole-body radionuclide bone scan for bone disease. Exception: Participants with soft tissue pelvic disease may be eligible (e.g., participants with enlarged lymph nodes below the aortic bifurcation (N1) are eligible if the short axis of the largest lymph node is \<20 mm)
* Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable with best available standard of care (incl. pads, drainage) are allowed
* Active clinically significant cardiac disease; history of seizure or condition that may pre-dispose to seizure which may require treatment with surgery or radiation therapy
* Prior therapy with: second generation anti-androgens (e.g., enzalutamide, apalutamide and darolutamide); CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone, ketoconazole; radiopharmaceutical agents (e.g., Strontium-89), PSMA-targeted radioligand therapy; immunotherapy (e.g., sipuleucel-T); chemotherapy, except if administered in the adjuvant/neoadjuvant setting, completed \> 2 years before randomization; any other investigational agents for CRPC; use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethimide) or first-generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) within 28 days before randomization; radiation therapy (external beam radiation therapy \[EBRT\] and brachytherapy within 28 days before randomization
* Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, biological therapy or investigational therapy

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: PSA response
timeFrame: From randomization until PSA nadir value of =< 0.2 ng/mL that is confirmed by a second (the next) PSA measurement >= 4 weeks later, up to 5 years
Secondary outcomes:
measure: Metastatic Free Survival (MFS)
timeFrame: From date of randomization until date of progression or date of death whichever occurs first, up to 5 years
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, up to 5 years
measure: Overall Survival (OS)
timeFrame: From date of randomization until date of death from any cause, up to 5 years
measure: second Progression Free Survival (PFS2)
timeFrame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 5 years
measure: Time to symptomatic progression
timeFrame: From date of randomization until development of a symptomatic skeletal event, new systemic anti-cancer therapy, surgical intervention or radiation therapy, whichever occurs first, up to 5 years
measure: Time to initiation of cytotoxic chemotherapy
timeFrame: From the date of randomization to the date of first documented dose of new cytotoxic chemotherapy administered to the participant, up to 5 years
measure: Time to first symptomatic skeletal event (TTSSE)
timeFrame: From the date of randomization to the date of the first new symptomatic pathological bone fracture, spinal cord compression, orthopedic surgical intervention, radiation therapy or death due to any cause, whichever occurs first, up to 5 years
measure: Time to distant metastasis development
timeFrame: From the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis, up to 5 years
measure: Time to local radiological progression
timeFrame: From the date of randomization to the date of first documented local radiographic disease progression, up to 5 years
measure: Time to initiation or change in therapy
timeFrame: From the date of randomization to the date of first dose of a new / change in therapy, up to 5 years
measure: Time to PSA response
timeFrame: From randomization to PSA response, up to 5 years
measure: PSA50 response
timeFrame: From date of randomization until end of efficacy follow-up, up to 5 years
measure: PSA90 response
timeFrame: From date of randomization until end of efficacy follow-up, up to 5 years
measure: Functional Assessment of Cancer Therapy - Prostate (FACT-P)
timeFrame: From date of randomization until end of efficacy follow-up, up to 5 years
measure: Functional Assessment of Cancer Therapy - Radiotherapies (FACT-RNT) Questionnaire
timeFrame: From date of randomization until end of efficacy follow-up, up to 5 years
measure: Brief Pain Inventory - Short Form (BPI-SF) Questionnaire
timeFrame: From date of randomization until end of efficacy follow-up, up to 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Urology Associates of Mobile
state: Alabama
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Athens
country: United States
facility: University Cancer and Blood Center LLC
state: Georgia
city: Des Moines
country: United States
facility: Unity Point Clinic
state: Iowa
city: Omaha
country: United States
facility: Urology Cancer Center PC
state: Nebraska
city: Syracuse
country: United States
facility: Associated Med Professionals of NY
state: New York
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: York
country: United States
facility: Wellspan York Hospital
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: Dallas
country: United States
facility: Urology Clinic of North Texas
state: Texas
city: Dallas
country: United States
facility: Univ of Texas Southwest Med Center
state: Texas
city: El Paso
country: United States
facility: Rio Grande Urology
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio Mays Cancer Center
state: Texas
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Beijing
country: China
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Angers 02
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Arnhem
country: Netherlands
facility: Novartis Investigative Site
state: Gelderland
city: Kielce
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Terrassa
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: