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CTRI Number  CTRI/2025/11/097691 [Registered on: 19/11/2025] Trial Registered Prospectively
Last Modified On: 17/02/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Radiation Therapy 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   To find out the effect of a new drug called AAA817 compared to standard treatment in patients with prostate cancer. 
Scientific Title of Study   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 
Trial Acronym  AcTFirst 
Secondary IDs if Any  
Secondary ID  Identifier 
2024-512340-32-00  EudraCT 
CAAA817B12301,v00,17-Jan-2025   Protocol Number 
NCT06855277  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Murugananthan K  
Designation  SSO Country Head  
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com   
 
Details of Contact Person
Scientific Query  
Name  Murugananthan K  
Designation  SSO Country Head  
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)


MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com   
 
Details of Contact Person
Public Query  
Name  Murugananthan K  
Designation  SSO Country Head  
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)


MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com   
 
Source of Monetary or Material Support  
Novartis Pharma AG, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd  
Address  7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla Complex, Bandra (East), Mumbai - 400051,lndia  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Australia
Austria
Belgium
Brazil
Canada
China
Czech Republic
France
Germany
Hong Kong
India
Italy
Japan
Mexico
Netherlands
Poland
Portugal
Republic of Korea
Singapore
Slovakia
Spain
Taiwan
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Prathap H J  Aster Whitefield Hospital  Dept. Nuclear Medicine, Sadaramangala, Plot No. 3 & 4, Main Road, off Whitefield, opposite ITPL Main Road, Industrial Area, Whitefield
Bangalore
KARNATAKA 		 9743258228

prathap.hj@asterhospital.in 
Dr Ishita Sen  Fortis Memorial Research Institute  Dept. Nuclear Medicine Fortis Memorial Research Institute Sec-44, opp. millenium city center metro station Gurugram HR-122002
Gurgaon
HARYANA 		 9811127080

ishita.sen@fortishealthcare.com 
Dr Venkatesh Rangarajan  Tata Memorial Hospital  Department of Nuclear Medicine & Molecular imaging, Tata Memorial Hospital, Dr. E. Borges road, Parel, Mumbai – 400012, Maharashtra, India.
Mumbai
MAHARASHTRA 		 9969014183

drvrangarajan@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Aster CMI Hospital Institutional Ethics Committee  Approved 
Ethics Committee for Research -Fortis Memorial Research Institute  Approved 
Institutional Ethics Committee I/II, Tata Memorial Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C61||Malignant neoplasm of prostate,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  AAA817 monotherapy  AAA817 will be injected into the vein, in cycles (cycle = 8 weeks). A dose of AAA817 will be given once at the beginning of each cycle for a minimum of 2 and maximum of 6 total doses (cycles) 
Intervention  AAA817+ARPI (Androgen receptor pathway inhibitors)  AAA817 will be injected into the vein, in cycles (cycle = 8 weeks). A dose of AAA817 will be given once at the beginning of each cycle for a minimum of 2 and maximum of 6 total doses (cycles). ARPI daily given in a tablet or capsule form and should be taken orally. 
Comparator Agent  Investigator’s choice of SoC  Taxane-based chemotherapy will be given through i.v. injection as per package insert/guidelines 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Male 
Details  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 and are eligible as determined by the sponsor’s central reading rules.
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), based on at least 1 of the following criteria:
Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines.
• Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)].
Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria Scher et al 2016).
 
 
ExclusionCriteria 
Details  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. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Radiographic Progression Free Survival (rPFS)  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  
Outcome  TimePoints 
Overall Survival (OS) (Key Secondary Endpoint)  From the date of randomization to the date of death due to any cause, assessed up to approximately 40 months. 
Radiographic Progression Free Survival by PSMA PET/CT and (rPSF-PET)(Key Secondary)  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. 
Progression Free Survival (PFS2)  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. 
Overall Response Rate (ORR)  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. 
Disease Control Rate (DCR)  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. 
Time to first radiographic soft tissue progression (TTSTP)  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. 
Time to first symptomatic skeletal event (TTSSE)  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. 
Prostate specific antigen response (PSA50 and PSA90)  From the date of randomization to the date of safety follow up, assessed up to approximately 40.0 months. 
Time-concentration profiles and PK parameters of AAA817  From Cycle 1 Day 1 up to approximately cycle 5 days 11 (each cycle is 8 weeks). 
Change from baseline on FACT-P Prostate Cancer Subscale (PCS)  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. 
Time to worsening on the Worst Pain  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. 
rPFS in participants treated with AAA817  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. 
OS in participants treated with AAA817  From the date of randomization to the date of death due to any cause assessed up to approximately 40.0 months. 
 
Target Sample Size   Total Sample Size="605"
Sample Size from India="14" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/12/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  31/07/2025 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="6"
Months="1"
Days="0" 
Recruitment Status of Trial (Global)   Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   The purpose of this study is to determine whether [225Ac]Ac-PSMA-617 (AAA817), given for up to 6 cycles at a dose of 10 Megabecquerel (MBq) +/- 10%, plus androgen receptor pathway inhibitor (ARPI), improves the radiographic progression free survival (rPFS) compared to investigator’s choice of standard of care (SOC) (ARPI change or taxane-based chemotherapy) in adult participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC) treated with another ARPI as last treatment and who have not been exposed to a taxane-containing chemotherapy in the mCRPC setting nor have received any prior PSMA-targeting radioligand therapy. 
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