Brief 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
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
Brief Title
Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-669-6682
Central Contact Email
novartis.email@novartis.com
Central Contact Role
Contact
Central Contact Phone
+41613241111
Completion Date
Completion Date Type
Estimated
Conditions
Prostate Cancer
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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
inclusion/
* 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
inclusion/
Gender
Male
Gender Based
false
Keywords
post [177Lu]Lu-PSMA targeted therapy
PSMA-positive
mCRPC adults
Metastatic castration-resistant prostate cancer
AAA817
[225Ac]Ac-PSMA-617
PSMA-based targeted therapy
Standard of Care
SOC
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT06780670
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CAAA817A12201
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement
Outcome Measure
Biochemical response rate (Phase II)
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Description
Safety defined as the type, incidence and severity of AEs and SAEs, and deaths
Outcome Measure
Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II
Outcome 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
Outcome Description
Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure
Outcome Measure
Tolerability of the proposed dose of AAA817- Phase II
Outcome 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
Outcome Description
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
Outcome Measure
Radiographic progression-free survival (rPFS)- Phase III
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Description
Percentage of participants who are alive or who are lost to follow-up at the time of analysis
Outcome Measure
Overall survival (OS)- Phase III
Outcome Time Frame
from date of randomization up to approximately 24 months
Secondary Ids
Secondary Id
2024-512342-42-00
Secondary Outcomes
Outcome Description
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Radiographic progression-free survival (rPFS)- Phase II
Outcome Description
Percentage of Participants meeting Progression Free Survival
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Progression free survival (PFS)- Phase II
Outcome Description
Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Overall response rate (ORR)- Phase II
Outcome Description
Percentage of participants with BOR of CR, PR, stable disease (SD) or non-CR/non-PD
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Disease control rate (DCR)- Phase II
Outcome Description
Percentage of participants who are alive or who are lost to follow-up at the analysis data cut-off
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Overall survival (OS)- Phase II
Outcome Description
Percentage of participants with PFS -defined as the time from date of randomization to first documented progression
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Progression free survival (PFS) -Phase III
Outcome Description
ORR is defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR)
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Overall response rate (ORR)- Phase III
Outcome Description
DCR is defined as the percentage of participants with BOR of confirmed CR, PR, stable disease (SD) or Non-CR/Non progressive disease (PD)
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Disease control rate (DCR) -Phase III
Outcome Description
Percentage of participants with confirmed DoR defined as duration of time between the date of first documented response (CR or PR) and progression or death due to any cause, whichever occurs first.
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Duration of response (DoR)- Phase III
Outcome Description
Percentage of participants with confirmed first radiographic progression in soft tissue
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Time to first radiographic soft tissue progression (TTSTP)- Phase III
Outcome Description
Percentage of participants with confirmed skeletal event is defined as new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurs first
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
First symptomatic skeletal event (TTSSE)_Phase III
Outcome Description
PSA50 is defined as the percentage of participants who achieved a confirmed ≥ 50% decrease from baseline
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Prostate specific antigen (PSA) response -Phase III
Outcome Description
Percentage of participants who had a Change from baseline on FACT-P Prostate Cancer Subscale (PCS)
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III
Outcome Description
Time to worsening on the Worst Pain defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (brief pain inventory - short form (BPI-SF)) of at least 30% of baseline or minimum of 2 points increase from baseline, or death due to any cause, whichever occurs first. BPI-SF is a self-reported questionnaire to evaluate pain intensity (severity) and impact of pain on the participant's daily functioning (interference).
Outcome Time Frame
from date of randomization up to approximately 24 months
Outcome Measure
Time to worsening on the Worst Pain: Phase III
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Prostate Cancer --- PROSTATIC NEOPLASMS
Genitourinary (GU) & Urologic Cancers --- GENITAL NEOPLASMS, MALE
Genitourinary (GU) & Urologic Cancers --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
MeSH Terms
PROSTATIC NEOPLASMS
GENITAL NEOPLASMS, MALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
GENITAL DISEASES, MALE
GENITAL DISEASES
UROGENITAL DISEASES
PROSTATIC DISEASES
MALE UROGENITAL DISEASES
(225)AC-PSMA-617