Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 2/Phase 3

PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

NCT ID: NCT06780670Sponsor: Novartis PharmaceuticalsLast updated: 2026-05-27

Summary

This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Detailed description

Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.

Arms & interventions

  • DrugInvestigators choice of SoC

    The control treatment in Phase III is investigator's choice of SoC

  • DrugAAA817

    The investigational treatment is AAA817

  • DrugAAA817

    The investigational treatment is AAA817

  • DrugAAA817

    Investigational treatment is the Dose B of AAA817

Outcome measures

Primary

  • Biochemical response rate (Phase II)

    Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement

    Time frame: from date of randomization up to approximately 24 months

  • Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II

    Safety defined as the type, incidence and severity of AEs and SAEs, and deaths

    Time frame: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later

  • Tolerability of the proposed dose of AAA817- Phase II

    Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure

    Time frame: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817

  • Radiographic progression-free survival (rPFS)- Phase III

    Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis

    Time frame: from date of randomization up to approximately 24 months

  • Overall survival (OS)- Phase III

    Percentage of participants who are alive or who are lost to follow-up at the time of analysis

    Time frame: from date of randomization up to approximately 24 months

Secondary

  • Radiographic progression-free survival (rPFS)- Phase II

    Time frame: from date of randomization up to approximately 24 months

  • Progression free survival (PFS)- Phase II

    Time frame: from date of randomization up to approximately 24 months

  • Overall response rate (ORR)- Phase II

    Time frame: from date of randomization up to approximately 24 months

  • Disease control rate (DCR)- Phase II

    Time frame: from date of randomization up to approximately 24 months

  • Overall survival (OS)- Phase II

    Time frame: from date of randomization up to approximately 24 months

  • Progression free survival (PFS) -Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Overall response rate (ORR)- Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Disease control rate (DCR) -Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Duration of response (DoR)- Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Time to first radiographic soft tissue progression (TTSTP)- Phase III

    Time frame: from date of randomization up to approximately 24 months

  • First symptomatic skeletal event (TTSSE)_Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Prostate specific antigen (PSA) response -Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III

    Time frame: from date of randomization up to approximately 24 months

  • Time to worsening on the Worst Pain: Phase III

    Time frame: from date of randomization up to approximately 24 months

Eligibility criteria

Sex: MaleAge: 18 Years to 100 YearsHealthy volunteers: No
Inclusion Criteria: ∙ * adults ≥ 18 years of age. * ECOG performance status of 0 to 2. * histopathological and/or cytological confirmation of adenocarcinoma of the prostate. * PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed, * castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L). * Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. * ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization * eGFR as requested by the sponsor Exclusion Criteria: * Any investigational agents within 28 days prior to the day of randomization. * Any 225Ac-based investigational compound used prior to the day of randomization. * Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. * Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury) * Baseline xerostomia ≥ Grade 2 by CTCAE v.5 * History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease * History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed). Other protocol-defined inclusion/exclusion criteria may apply.

Study locations (27)

VA Greater LA Healthcare System

Los Angeles, California, 90073

Recruiting
Janake Wijesuriya · Contact
Gholam Reza Berenji · Principal Investigator

VA Palo Alto Health Care System

Palo Alto, California, 94304-1207

Recruiting
Niko Del Mar · Contact
Minal Vasanawala · Principal Investigator

Stanford University Medical Center

Palo Alto, California, 94304

Recruiting
Mikayla Easterling · Contact
Hong Song · Principal Investigator

Sansum Clinic

Santa Barbara, California, 93105

Recruiting
Gregg Newman · Principal Investigator

Saint Johns Cancer Institute

Santa Monica, California, 90404

Recruiting
Przemyslaw Twardowski · Principal Investigator

Hartford Hospital

Hartford, Connecticut, 06102

Recruiting
Melanie Manning · Contact
Andrew Salner · Principal Investigator

AdventHealth

Orlando, Florida, 32804

Recruiting
Ravi Shridhar · Principal Investigator

University Cancer and Blood Center LLC

Athens, Georgia, 30607

Recruiting
Christen Nicole Cooper Pope · Contact
Petros Nikolinakos · Principal Investigator

Emory University

Atlanta, Georgia, 30322

Recruiting
Shahid Sattar Ahmed. · Principal Investigator

Indiana University

Indianapolis, Indiana, 46202

Recruiting
Marie Burton · Contact
Nabil Adra · Principal Investigator

University of Kansas Hospital

Kansas City, Kansas, 66160

Recruiting
Kelsey Schwensen · Contact
Xinglei Shen · Principal Investigator

East Jefferson Hospital

Metairie, Louisiana, 70006

Recruiting
Alexandra Lieberman · Contact
Alton Oliver Sartor · Principal Investigator

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

Recruiting
Xiao Wei. · Principal Investigator

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
Ooviya Sathiyamoorthy · Contact
David J Einstein · Principal Investigator

WA Uni School Of Med

St Louis, Missouri, 63110

Recruiting
Collin Welch · Contact
Jeff Michalski · Principal Investigator

Nebraska Cancer Specialists

Omaha, Nebraska, 68154

Recruiting
Marlene Bridwell · Contact
Samuel Mehr · Principal Investigator

New Jersey Urology LLC

Voorhees Township, New Jersey, 08043

Recruiting
Gabriela Mercado · Contact
Gordon Brown · Principal Investigator

Associated Med Professionals of NY

Syracuse, New York, 13210

Recruiting
Nathan Forrest · Contact
Steven Finkelstein · Principal Investigator

Montefiore Medical Center

The Bronx, New York, 10467

Recruiting
Tahrima Chowdhury · Contact
Benjamin A Gartrell · Principal Investigator

Central Ohio Urology Group

Gahanna, Ohio, 43230

Recruiting
Sarah Faisal · Contact
Benjamin Martin · Principal Investigator

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Recruiting
Candice Schewbel · Contact
Matthew Zibelman · Principal Investigator

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572

Recruiting
Neal D Shore · Principal Investigator

Texas Oncology

Dallas, Texas, 75251

Recruiting
Michael P Herman · Principal Investigator

Urology San Antonio

San Antonio, Texas, 78229

Recruiting
Sandra Davila · Contact
Daniel Saltzstein · Principal Investigator

Utah Intermountain Medical Center

Murray, Utah, 84107

Recruiting
Becky Arroyo · Contact
David Gill · Principal Investigator

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024

Recruiting
Brianna Woo · Contact
Ruben Raychaudhuri · Principal Investigator

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting
Nadia Thomas · Contact
Deepak Kilari · Principal Investigator