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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06855277




Registration number
NCT06855277
Ethics application status
Date submitted
18/02/2025
Date registered
3/03/2025
Date last updated
5/09/2025

Titles & IDs
Public title
Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC
Scientific title
A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer
Secondary ID [1] 0 0
2024-512340-32-00
Secondary ID [2] 0 0
CAAA817B12301
Universal Trial Number (UTN)
Trial acronym
AcTFirst
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AAA817
Treatment: Drugs - ARPI
Treatment: Drugs - Standard of Care

Experimental: Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) - Participants will receive AAA817 infusion directly into a vein with ARPIs.

Experimental: Investigational Arm: AAA817 - Participants will receive AAA817 infusion directly into a vein.

Active comparator: Control arm: Investigator's choice of SoC (ARPI or taxane-based chemotherapy) - Participants will receive standard treatment as decided by the trial doctor either as a chemotherapy infusion directly into a vein or ARPI either as capsules or tablets.


Treatment: Drugs: AAA817
AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits radiation to kill them. This treatment is also called a radioligand therapy.

Treatment: Drugs: ARPI
Androgen receptor pathway inhibitor (ARPI): An ARPI is approved for the treatment of prostate cancer. It works by blocking signals from male hormones, such as testosterone, that helps cancer cells grow. By blocking these signals, an ARPI slows down or stops the growth of prostate cancer cells. In this trial, participants will be given either enzalutamide or abiraterone.

Treatment: Drugs: Standard of Care
Standard treatment includes approved treatment for mCRPC. In this trial, the trial doctor will decide which available treatment participants will receive. The trial doctor will select either an ARPI of enzalutamide or abiraterone, or a taxane based chemotherapy of docetaxel or cabazitaxel.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Progression Free Survival (rPFS)
Timepoint [1] 0 0
From the date of randomization to the date of the first documented radiographic disease progression using conventional imaging, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [1] 0 0
Overall Survival (OS) (Key Secondary Endpoint)
Timepoint [1] 0 0
From the date of randomization to the date of death due to any cause, assessed up to approximately 40 months.
Secondary outcome [2] 0 0
Radiographic Progression Free Survival by PSMA PET/CT and (rPSF-PET)(Key Secondary)
Timepoint [2] 0 0
From date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
From date of randomization to the first documented progression by investigator's assessment or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [4] 0 0
Progression Free Survival (PFS2)
Timepoint [4] 0 0
From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to approximately 40.0 months.
Secondary outcome [5] 0 0
Overall Response Rate (ORR)
Timepoint [5] 0 0
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [6] 0 0
Disease Control Rate (DCR)
Timepoint [6] 0 0
From the date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [7] 0 0
Duration of Response (DoR)
Timepoint [7] 0 0
From the date of first documented response (CR or PR) for confirmed responders and the date of first documented radiographic progression in soft tissue or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [8] 0 0
Time to first radiographic soft tissue progression (TTSTP)
Timepoint [8] 0 0
From the date of randomization to the date of radiographic soft tissue progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [9] 0 0
Time to first symptomatic skeletal event (TTSSE)
Timepoint [9] 0 0
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [10] 0 0
Prostate specific antigen response (PSA50 and PSA90)
Timepoint [10] 0 0
From the date of randomization to the date of safety follow up, assessed up to approximately 40.0 months.
Secondary outcome [11] 0 0
Time-concentration profiles and PK parameters of AAA817
Timepoint [11] 0 0
From Cycle 1 Day 1 up to approximately cycle 5 days 11 (each cycle is 8 weeks).
Secondary outcome [12] 0 0
Change from baseline on FACT-P Prostate Cancer Subscale (PCS)
Timepoint [12] 0 0
From randomization to the first occurrence of worsening on the score or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [13] 0 0
Time to worsening on the Worst Pain
Timepoint [13] 0 0
From randomization to the first occurrence of worsening from baseline, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [14] 0 0
rPFS in participants treated with AAA817
Timepoint [14] 0 0
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary outcome [15] 0 0
OS in participants treated with AAA817
Timepoint [15] 0 0
From the date of randomization to the date of death due to any cause assessed up to approximately 40.0 months.

Eligibility
Key inclusion criteria
Key

* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults = 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI).

Key
Minimum age
18 Years
Maximum age
100 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with any approved or investigational RLT, approved or investigational radioisotopes
* Previous treatment with any conventional external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
* Participants with known or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.
* Any approved or investigational agents/systemic anti-cancer therapy (e.g. other chemotherapy, investigational therapy, immunotherapy or biological therapy including monoclonal antibodies) within 28 days (or 5 times the half-life of that therapy whichever is longer) of the anticipated day C1D1.
* Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/11/2032
Actual
Sample size
Target
605
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Adelaide
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Sichuan
Country [2] 0 0
China
State/province [2] 0 0
Guangzhou
Country [3] 0 0
China
State/province [3] 0 0
Wuhan
Country [4] 0 0
Japan
State/province [4] 0 0
Hokkaido
Country [5] 0 0
Singapore
State/province [5] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06855277