Prostate CancerPhase 3AcTFirstNCT06855277
Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC
A Phase 3 study testing AAA817 and ARPI in people with Prostate Cancer, run by Novartis Pharmaceuticals at 106 sites in 12 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- AAA817 and ARPI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 940 participants
- Where
- 106 sitesin 12 countries
- Study dates
- 1 Jul 2025to 4 Nov 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
- Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
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- 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).
- Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.
Who cannot join
- Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, [177Lu]Lu-PSMA, [177Lu]-DOTA, or Radium- 223.)
- Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
- Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.
- Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
106 sites in 12 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
106 sites in 12 countries
United States42 sites, 42 recruiting
- Recruiting
New Mexico Oncology Hematology
Albuquerque, New Mexico, 87109
Kimberly Demos, +1 505 822 3869#3867, kimberlyd@nmohc.com
Gregg Franklin
- Recruiting
University Cancer and Blood Center LLC
Athens, Georgia, 30607
Mary Egan, 706-353-2990, mary.egan@universitycancer.com
Gordon Schoenfeld
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Noura Radwan, nradwan1@jhmi.edu
Ana Kiess
- Recruiting
Beth Israel Deaconess Med Center
Boston, Massachusetts, 02215
Katerina von Helms, 617-667-7000, kvonhelm@bidmc.harvard.edu
Glenn Bubley
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Amanda Lilienfeld, amanda_lilienfeld@dfci.harvard.edu
Xiao Wei
- Recruiting
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Alex Jones, joalex@musc.edu
Kevin Becker
- Recruiting
Tennessee Oncology PLLC
Chattanooga, Tennessee, 37404
Mercedes Bruce, mbruce@tnonc.com
Katy Beckermann
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Rachel Hanna Springsdorf, +1 312 695 1382, rachelspringsdorf@northwestern.edu
Maha Hussain
- Recruiting
University of Illinois Cancer Center at Chicago
Chicago, Illinois, 60612
Ethan Gu, 312-413-2746, egu3@uic.edu
Natalie Reizine
- Recruiting
Urology Group - Solaris Network
Cincinnati, Ohio, 45212
William Corbett, wcorbett@urologygroup.com
Marc Pliskin
- Recruiting
Bassett Medical Center
Cooperstown, New York, 13326
Peggy Cross, peggy.cross@bassett.org
Timothy Korytko
- Recruiting
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Bethany Glatthar, 303-839-6530, Bethany.Glatthar@usoncology.com
Allen Cohn
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
Kimberlee Dobson, 313-576-9454, dobsonk@karmanos.org
Nitin Vaishampayan
- Recruiting
Astera Cancer Center
East Brunswick, New Jersey, 08816
Allison Cabinian, allison.cabinian@asterahealthcare.org
Phillip D Reid
- Recruiting
Florida Cancer Specialists
Fort Myers, Florida, 33901
Julie Kara, jkara@flcancer.com
Bradford Perez
- Recruiting
Central Ohio Urology Group
Gahanna, Ohio, 43230
Sam Carey, Sam.Carey@centralohiourology.com
Benjamin Martin
- Recruiting
Urology Centers Of Alabama Pc
Homewood, Alabama, 35209
Meredith Sharpton, msharpton@urologyal.com
Bryant Poole
- Recruiting
Univ Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242
Kellie Bodeker, kellie-bodeker@uiowa.edu
Kristin Plichta
- Recruiting
University of Kansas Hospital
Kansas City, Kansas, 66160
Collin Bruey, cbruey@kumc.edu
Xinglei Shen
- Recruiting
Urology Austin
Lakeway, Texas, 78738
Christine Chau, christine.chau@urologyaustin.com
Brian Mazzarella
- Recruiting
East Jefferson Hospital
Metairie, Louisiana, 70006
Alexandra Lieberman, alexandra.lieberman@lcmchealth.org
Alton Oliver Sartor
- Recruiting
Baptist Health South
Miami, Florida, 33173
Leslie Castaneda, leslie.castaneda@baptisthealth.net
Rohan Garje
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Mariah Ziegler, 414-805-5249, mziegler@mcw.edu
Deepak Kilari
- Recruiting
West Virginia University Hospital
Morgantown, West Virginia, 26506
Nina Moore, nina.moore@hsc.wvu.edu
Raheel Siddiqui
- Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Rebecca Floyd, 843-839-1679, rebecca.floyd@startresearch.com
Neal D Shore
- Recruiting
Weill Cornell Medicine NY-Presb
New York, New York, 10021
Sarah Yuan, 646-962-2535, say7008@med.cornell.edu
Scott Tagawa
- Recruiting
Nebraska Cancer Specialists
Omaha, Nebraska, 68154
Marlene Bridwell, mbridwell@nebraskacancer.com
Samuel Mehr
- Recruiting
Univ Cali Irvine ALS Neuromuscular
Orange, California, 92868
Amanda Macaraeg, 714-456-2332, macaraeg@hs.uci.edu
Arash Rezazadeh Kalebasty
- Recruiting
AdventHealth
Orlando, Florida, 32804
Joseph Guzzo, 407-303-3235, joseph.guzzo@adventhealth.com
Ravi Shridhar
- Recruiting
Stanford University Medical Center
Palo Alto, California, 94304
Tiffany Chen, tiff1221@stanford.edu
Hong Song
- Recruiting
University of Rochester Medical Ctr
Rochester, New York, 14642
Therese Smudzin, Therese_Smudzin@urmc.rochester.edu
Haoming Carl Qiu
- Recruiting
Urology San Antonio
San Antonio, Texas, 78229
Sandra Davila, sandra.davila@usa-clinicaltrials.com
Daniel Saltzstein
- Recruiting
Sansum Clinic
Santa Barbara, California, 93105
Megan Martinez, 805-563-5800, megan.martinez@sutterhealth.or
Mukul Gupta
- Recruiting
New England Cancer Specialists
Scarborough, Maine, 04074
Abigail Berard, berara@newecs.org
Christian Anton Thomas
- Recruiting
Swedish Medical Center
Seattle, Washington, 98122-4379
Brianna McNealley, 855-922-6237, brianna.mcnealley@swedish.org
Song Zhao
- Recruiting
Wash U School of Medicine
St Louis, Missouri, 63110
Collin Welch, c.welch@wustl.edu
Jeff Michalski
- Recruiting
Associated Med Professionals of NY
Syracuse, New York, 13210
Nathan Forrest, nathan.forrest@ampofny.com
Steven Finkelstein
- Recruiting
Northwest Medical Specialties
Tacoma, Washington, 98405
Patricia Walsh, pwalsh@nwmsonline.com
Li Zhang
- Recruiting
Montefiore Medical Center
The Bronx, New York, 10461
Tahrima Chowdhury, 718-920-2680, tahchowdhu@montefiore.org
Benjamin A Gartrell
- Recruiting
Woodlands Cancer Institute American Oncology Partners
The Woodlands, Texas, 77384
Brittany Rogers, brittany.rogers@aoncology.com
Jason Berilgen
- Recruiting
University of Arizona
Tucson, Arizona, 85724
Jeanette Cardenas, 520-626-2340, serranoj@arizona.edu
Bital Savir-Baruch
- Recruiting
New Jersey Urology LLC
Voorhees Township, New Jersey, 08043
Gabriela Mercado, 856-673-1613, gmercado3@nj-urology.com
Gordon Brown
China19 sites, 19 recruiting
- Recruiting
Novartis Investigative Site
Beijing, 100034
- Recruiting
Novartis Investigative Site
Beijing, 100036
- Recruiting
Novartis Investigative Site
Chengdu, Sichuan, 610041
- Recruiting
Novartis Investigative Site
Fuzhou, Fujian, 350025
- Recruiting
Novartis Investigative Site
Guangzhou, Guangdong, 510120
- Recruiting
Novartis Investigative Site
Guangzhou, Guangdong, 510632
- Recruiting
Novartis Investigative Site
Guangzhou, 510060
- Recruiting
Novartis Investigative Site
Hangzhou, Zhejiang, 310007
- Recruiting
Novartis Investigative Site
Hangzhou, Zhejiang, 310022
- Recruiting
Novartis Investigative Site
Nanjing, Jiangsu, 210006
- Recruiting
Novartis Investigative Site
Nanjing, Jiangsu, 210029
- Recruiting
Novartis Investigative Site
Shanghai, 200001
- Recruiting
Novartis Investigative Site
Shanghai, 200025
- Recruiting
Novartis Investigative Site
Shanghai, 200032
- Recruiting
Novartis Investigative Site
Shenyang, Liaoning, 110011
- Recruiting
Novartis Investigative Site
Tianjin, 300300
- Recruiting
Novartis Investigative Site
Tianjin, 300480
- Recruiting
Novartis Investigative Site
Wuhan, Hubei, 430022
- Recruiting
Novartis Investigative Site
Wuhan, Hubei, 430030
Japan15 sites, 15 recruiting
- Recruiting
Novartis Investigative Site
Chiba, 2608717
- Recruiting
Novartis Investigative Site
Chuo Ku, Tokyo, 1040045
- Recruiting
Novartis Investigative Site
Fukuoka, 8110213
- Recruiting
Novartis Investigative Site
Fukuoka, 8120033
- Recruiting
Novartis Investigative Site
Fukuoka, 8128582
- Recruiting
Novartis Investigative Site
Fukushima, 9601295
- Recruiting
Novartis Investigative Site
Hiroshima, 7348551
- Recruiting
Novartis Investigative Site
Kamakura, Kanagawa, 2478533
- Recruiting
Novartis Investigative Site
Kobe, Hyōgo, 6500017
- Recruiting
Novartis Investigative Site
Kobe, Hyōgo, 6500047
- Recruiting
Novartis Investigative Site
Kumamoto, Kumamoto, 8608556
- Recruiting
Novartis Investigative Site
Kyoto, 6068507
- Recruiting
Novartis Investigative Site
Nagoya, Aichi-ken, 4668560
- Recruiting
Novartis Investigative Site
Sapporo, Hokkaido, 0608648
- Recruiting
Novartis Investigative Site
Yokohama, Kanagawa, 2360004
South Korea6 sites, 6 recruiting
- Recruiting
Novartis Investigative Site
Seoul, 01812
- Recruiting
Novartis Investigative Site
Seoul, 03080
- Recruiting
Novartis Investigative Site
Seoul, 03722
- Recruiting
Novartis Investigative Site
Seoul, 05505
- Recruiting
Novartis Investigative Site
Seoul, 06351
- Recruiting
Novartis Investigative Site
Seoul, 06591
Australia5 sites, 5 recruiting
- Recruiting
Novartis Investigative Site
Adelaide, South Australia, 5000
- Recruiting
Novartis Investigative Site
Adelaide, 5000
- Recruiting
Novartis Investigative Site
Darlinghurst, New South Wales, 2010
- Recruiting
Novartis Investigative Site
Malvern, Victoria, 3144
- Recruiting
Novartis Investigative Site
Murdoch, Western Australia, 6150
Taiwan5 sites, 5 recruiting
- Recruiting
Novartis Investigative Site
Kaohsiung City, 833
- Recruiting
Novartis Investigative Site
Taichung, 407219
- Recruiting
Novartis Investigative Site
Tainan, 704302
- Recruiting
Novartis Investigative Site
Taipei, 10002
- Recruiting
Novartis Investigative Site
Taoyuan, 33305
United Kingdom4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
London, EC1A 7BE
- Recruiting
Novartis Investigative Site
Oxford, Oxfordshire, OX4 6LB
- Recruiting
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
- Recruiting
Novartis Investigative Site
Windsor, Surrey, SL4 3HD
India3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Bengaluru, Karnataka, 560066
- Recruiting
Novartis Investigative Site
Gurgaon, Haryana, 122002
- Recruiting
Novartis Investigative Site
Mumbai, Maharashtra, 400012
Singapore3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Singapore, 119074
- Recruiting
Novartis Investigative Site
Singapore, 168583
- Recruiting
Novartis Investigative Site
Singapore, 169608
Brazil2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
São Paulo, São Paulo, 01308-050
- Recruiting
Novartis Investigative Site
São Paulo, São Paulo, 05652-000
Hong Kong1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Hong Kong, 999077
Mexico1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Mexico City, 03330
About this study
Official 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
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 or [177Lu]Lu-PSMA-617 (AAA617)) 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.
Read the detailed description
This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or [177Lu]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS).
Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.
Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.
Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or [177Lu]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.
Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).
Safety will be assessed routinely during the study. Crossover is not allowed among study arms.
The study will be conducted in the USA among other countries globally.
- Conditions
- Prostate Cancer
- Being tested
- AAA817, ARPI, Standard of Care
- Keywords
- Positive Metastatic Castration Resistant Prostate Cancer, PSMA, PSMA-positive, AAA817, [225AC] AC-PSMA-617, Radioligand Therapy, RLT, Androgen receptor pathway inhibitor, ARPI, Taxane, Metastatic castration resistant prostate cancer, mCRPC, AcTFirst, [177Lu]Lu- PSMA-617, AAA617
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAA817Drug
Also called [225Ac]Ac-PSMA-617
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.
ARPIDrug
Also called Enzalutamide or Abiraterone
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.
Standard of CareDrug
Also called ARPI enzalutamide, ARPI abiraterone, Taxane based chemotherapy of docetaxel, Taxane based chemotherapy of cabazitaxel
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 or [177Lu]Lu-PSMA-617 (AAA617).
| Study group | Role | What they receive |
|---|---|---|
| Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) | Experimental | Participants will receive AAA817 infusion directly into a vein with ARPIs. Receives: Drug: AAA817; Drug: ARPI |
| Investigational Arm: AAA817 | Experimental | Participants will receive AAA817 infusion directly into a vein. Receives: Drug: AAA817 |
| Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617) | Active comparator | Participants will receive standard treatment as decided by the trial doctor either as a taxane-based chemotherapy infusion directly into a vein or ARPI change either as capsules or tablets or AAA617 monotherapy infusion directly into a vein. Receives: Drug: ARPI; Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiographic Progression Free Survival (rPFS)
Time to radiographic disease progression or death due to any cause.
Measured: 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 outcomes (15)
Overall Survival (OS) (Key Secondary Endpoint)
Time to death due to any cause.
Measured: 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 by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 (Key Secondary)
Time to radiographic disease progression, using by blinded independent central review (BICR) using conventional imaging and Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 criteria or death due to any cause.
Measured: 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.
Overall Survival in participants with PSMA-positive mCRPC treated with another ARPI. (Key Secondary)
Time to death due to any cause.
Measured: From the date of randomization to the date of death due to any cause.
rPFS in participants treated with AAA817
rPFS time to the date of first documented radiographic disease progression or death due to any cause, whichever occurs first.
Measured: 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.
Progression Free Survival (PFS)
Time to first documented progression or death due to any cause.
Measured: 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.
Progression Free Survival (PFS2)
Time to first documented progression on next line of antineoplastic therapy or death from any cause.
Measured: 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)
The proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue.
Measured: 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)
The proportion of participants with BOR of confirmed CR, PR, stable disease (SD) or non-CR/non-progressive disease (PD) in soft tissue.
Measured: 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.
Duration of Response (DoR)
Time between the date of first documented response and the date of first documented radiographic progression or death due to any cause.
Measured: 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.
Time to first radiographic soft tissue progression (TTSTP)
Time to radiographic soft tissue progression.
Measured: 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)
Time to date of first new symptomatic skeletal event of death due to any cause.
Measured: 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)
The percentage of participants who achieved ≥ 50% and ≥ 90% decrease from baseline, respectively.
Measured: 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
Time-concentration profiles and PK parameters of AAA817 (e.g. AUC, Cmax).
Measured: 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)
Change from baseline on FACT-P Prostate Cancer Subscale (PCS). FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment.
Measured: 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
Time to worsening on the Worst Pain is defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (BPI-SF) or death due to any cause, whichever occurs first.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2025
- Study start1 Jul 2025
- Primary completion29 Sep 2028 (estimated)
- Study completion4 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 940 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06855277
- Sponsor's protocol ID
- CAAA817B12301
- Other IDs
- 2024-512340-32
- Acronym
- AcTFirst
- Status last verified
- Oct 2026
- First submitted
- 18 Feb 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06855277
- Acronym / sponsor ID
- AcTFirst / CAAA817B12301
- Conditions
- Prostate Cancer
- Keywords
- Positive Metastatic Castration Resistant Prostate Cancer, PSMA, PSMA-positive, AAA817, [225AC] AC-PSMA-617, Radioligand Therapy, RLT, Androgen receptor pathway inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 940 participants (estimated)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 29 Sep 2028 (estimated)
- Study completion
- 4 Nov 2032 (estimated)
- First posted
- 3 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 or [177Lu]Lu-PSMA-617 (AAA617)) 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.
Detailed description
This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or [177Lu]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS).
Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.
Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.
Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or [177Lu]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.
Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).
Safety will be assessed routinely during the study. Crossover is not allowed among study arms.
The study will be conducted in the USA among other countries globally.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) | Experimental | Drug: AAA817, Drug: ARPIParticipants will receive AAA817 infusion directly into a vein with ARPIs. |
| Investigational Arm: AAA817 | Experimental | Drug: AAA817Participants will receive AAA817 infusion directly into a vein. |
| Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617) | Active comparator | Drug: ARPI, Drug: Standard of CareParticipants will receive standard treatment as decided by the trial doctor either as a taxane-based chemotherapy infusion directly into a vein or ARPI change either as capsules or tablets or AAA617 monotherapy infusion directly into a vein. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
Key exclusion criteria (5 listed)
- Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, [177Lu]Lu-PSMA, [177Lu]-DOTA, or Radium- 223.)
- Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
- Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.
- Other protocol-defined inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAA817Also: [225Ac]Ac-PSMA-617AAA817 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. | Drug | Investigational Arm: AAA817, Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) |
| ARPIAlso: Enzalutamide or AbirateroneAndrogen 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. | Drug | Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617), Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) |
| Standard of CareAlso: ARPI enzalutamide, ARPI abiraterone, Taxane based chemotherapy of docetaxel, Taxane based chemotherapy of cabazitaxelStandard 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 or [177Lu]Lu-PSMA-617 (AAA617). | Drug | Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617) |
Primary outcome
Radiographic Progression Free Survival (rPFS)
Time frame: 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.
Time to radiographic disease progression or death due to any cause.
15 secondary outcomes
Overall Survival (OS) (Key Secondary Endpoint)
Time frame: 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 by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 (Key Secondary)
Time frame: 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.
Overall Survival in participants with PSMA-positive mCRPC treated with another ARPI. (Key Secondary)
Time frame: From the date of randomization to the date of death due to any cause.
rPFS in participants treated with AAA817
Time frame: 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.
Progression Free Survival (PFS)
Time frame: 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.
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 approximately 40.0 months.
Overall Response Rate (ORR)
Time frame: 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)
Time frame: 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.
Duration of Response (DoR)
Time frame: 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.
Time to first radiographic soft tissue progression (TTSTP)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Novartis Pharmaceuticals contact
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
106 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AAA817 and ARPI in people with Prostate Cancer, run by Novartis Pharmaceuticals at 106 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 106 sites in United States, China, Japan, South Korea, Australia and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Novartis Pharmaceuticals (1-888-669-6682, novartis.email@novartis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiographic Progression Free Survival (rPFS) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.