A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC (PSMACare)

March 21, 2024 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Novartis Investigative Site
    • CZE
      • Olomouc, CZE, Czechia, 779 00
        • Recruiting
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Novartis Investigative Site
      • Krakow, Poland, 31-501
        • Recruiting
        • Novartis Investigative Site
      • Singapore, Singapore, 119228
        • Recruiting
        • Novartis Investigative Site
      • Singapore, Singapore, 169608
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Recruiting
        • Novartis Investigative Site
    • Andalucia
      • Granada, Andalucia, Spain, 18014
        • Recruiting
        • Novartis Investigative Site
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Recruiting
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Recruiting
        • Novartis Investigative Site
    • Galicia
      • Vigo, Galicia, Spain, 36204
        • Recruiting
        • Novartis Investigative Site
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Urology Cancer Center PC
        • Principal Investigator:
          • Luke Nordquist
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium [177Lu] vipivotide tetraxetan) once every 6 weeks for 6 cycles. ADT must be ongoing; Best supportive care is allowed.
Administration intravenously once every 6 weeks (1 cycle) for 6 cycles
Other Names:
  • 177Lu-PSMA-617
  • Lutetium [177Lu] vipivotide tetraxetan
Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans
Other Names:
  • 68Ga-PSMA-11
Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans
as prescribed by the local investigator
as prescribed by the local investigator
Experimental: Arm B
Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium [177Lu] vipivotide tetraxetan) once every 6 weeks for 6 cycles. In addition of SOC (ADT plus choice of ARPI as per physician's decision), Best supportive care is allowed.
Administration intravenously once every 6 weeks (1 cycle) for 6 cycles
Other Names:
  • 177Lu-PSMA-617
  • Lutetium [177Lu] vipivotide tetraxetan
Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans
Other Names:
  • 68Ga-PSMA-11
Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans
as prescribed by the local investigator
as prescribed by the local investigator
Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA response
Time Frame: 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
PSA response is defined as the time of PSA nadir value of =< 0.2 ng/mL is confirmed by a second (the next) PSA measurement at least 4 weeks later
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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, up to 5 years
rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression by conventional imaging assessed using RECIST 1.1 or death.
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, up to 5 years
Overall Survival (OS)
Time Frame: From date of randomization until date of death from any cause, up to 5 years
OS defined as date of death due to any cause
From date of randomization until date of death from any cause, up to 5 years
second Progression Free Survival (PFS2)
Time Frame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 5 years
PFS2 defined as time from the date of randomization to the date of first documented disease progression by investigator's assessment (PSA, radiographic, symptomatic, or any combination) on next line of therapy subsequent to MFS event or death due to any cause, whichever occurs first
From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 5 years
Time to symptomatic progression
Time Frame: 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

Time to symptomatic progression will be defined as the time from the date of randomization to the date of first documented event for any of the following:

  • Development of a symptomatic skeletal event (SSE)
  • Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy
  • Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy
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
Time to initiation of cytotoxic chemotherapy
Time Frame: From the date of randomization to the date of first documented dose of new cytotoxic chemotherapy administered to the participant, up to 5 years
Time to initiation of cytotoxic chemotherapy will be defined as the time from the date of randomization to the date of first documented dose of new cytotoxic chemotherapy being administered to the participant
From the date of randomization to the date of first documented dose of new cytotoxic chemotherapy administered to the participant, up to 5 years
Time to first symptomatic skeletal event (TTSSE)
Time Frame: 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
TTSSE is defined as the time from the date of randomization to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death due to any cause, whichever occurs first
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
Time to distant metastasis development
Time Frame: From the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis, up to 5 years
Time to distant metastasis development is defined as the time from the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1
From the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis, up to 5 years
Time to local radiological progression
Time Frame: From the date of randomization to the date of first documented local radiographic disease progression, up to 5 years
Time to local radiological progression is defined as the time from the date of randomization to the date of first documented local radiographic disease progression by conventional imaging using RECIST 1.1
From the date of randomization to the date of first documented local radiographic disease progression, up to 5 years
Time to initiation or change in therapy
Time Frame: From the date of randomization to the date of first dose of a new / change in therapy, up to 5 years
Time to initiation or change in therapy is defined as the time from the date of randomization to the date of first documented dose of a new / change in therapy being administered to the participant
From the date of randomization to the date of first dose of a new / change in therapy, up to 5 years
Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Time Frame: From date of randomization until end of efficacy follow-up, up to 5 years
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.
From date of randomization until end of efficacy follow-up, up to 5 years
Functional Assessment of Cancer Therapy - Radiotherapies (FACT-RNT) Questionnaire
Time Frame: From date of randomization until end of efficacy follow-up, up to 5 years
The FACT-RNT is assessing treatment-related symptoms of special interest/associated with Radionuclides Therapies. The FACT-RNT contains 15 items assessing dry mouth, dry eyes, difficulty urinating, nausea, vomiting, diarrhea, constipation, loss of appetite, fatigue, impact of fatigue, pain, bone pain, pain interference, bothered by of side effects of treatment and isolation due to illness or treatment.
From date of randomization until end of efficacy follow-up, up to 5 years
Brief Pain Inventory - Short Form (BPI-SF) Questionnaire
Time Frame: From date of randomization until end of efficacy follow-up, up to 5 years
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.
From date of randomization until end of efficacy follow-up, up to 5 years
Metastatic Free Survival (MFS)
Time Frame: From date of randomization until date of progression or date of death whichever occurs first, up to 5 years
MFS is defined as the time from date of randomization to the first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1 or death.
From date of randomization until date of progression or date of death whichever occurs first, up to 5 years
Time to PSA response
Time Frame: From randomization to PSA response, up to 5 years
Time to PSA response is calculated as the time from randomization to PSA response with a PSA nadir value of =< 0.2ng/mL.
From randomization to PSA response, up to 5 years
PSA50 response
Time Frame: From date of randomization until end of efficacy follow-up, up to 5 years
PSA50 response is defined as the proportion of participants who have a >= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement >= 4 weeks later
From date of randomization until end of efficacy follow-up, up to 5 years
PSA90 response
Time Frame: From date of randomization until end of efficacy follow-up, up to 5 years
PSA90 response is defined as the proportion of participants who have a >= 90% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement >= 4 weeks later
From date of randomization until end of efficacy follow-up, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2024

Primary Completion (Estimated)

February 23, 2029

Study Completion (Estimated)

February 23, 2029

Study Registration Dates

First Submitted

April 27, 2023

First Submitted That Met QC Criteria

April 27, 2023

First Posted (Actual)

May 8, 2023

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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