AzTrials
AzTrials

Prostatic NeoplasmsPhase 3PSMAdditionNCT04720157

An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care (SoC), Versus SoC Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

A Phase 3 study testing 177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT in people with Prostatic Neoplasms, run by Novartis Pharmaceuticals at 167 sites in 19 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care (SOC), versus Standard of Care alone, in adult male patients with Metastatic hormone sensitive prostate cancer (mHSPC). Read more about this study

Who is it for?
Ages 18 to 100 years, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,140 participants
Where
167 sitesin 19 countries
Study dates
9 Jun 2021to 11 Feb 2027
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

  • Participants eligible for inclusion in this study must meet all of the following criteria:
  • Signed informed consent must be obtained prior to participation in the study
  • Patients must be adults ≥18 years of age
  • Patients must have an ECOG performance status of 0 to 2
  • Patients must have a life expectancy >9 months as determined by the study investigator
  • Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
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  • Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
  • Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
  • Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
  • Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
  • Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
  • Patients must have adequate organ function:
  • Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
  • Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
  • Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
  • Albumin ≥2.5 g/dL
  • Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
  • Patients must be:
  • Treatment naïve OR minimally treated with:
  • Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
  • If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
  • Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.

Who cannot join

  • Participants meeting any of the following criteria are not eligible for inclusion in this study.
  • Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
  • Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
  • Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
  • Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
  • Ongoing participation in any other clinical trial
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  • Use of other investigational drugs within 30 days prior to day of randomization
  • Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
  • Transfusion for the sole purpose of making a participant eligible for study inclusion
  • Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
  • Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
  • Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
  • Active clinically significant cardiac disease defined as any of the following:
  • NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.
  • History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
  • History of familial long QT syndrome or known family history of Torsades de Pointes
  • Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
  • History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
  • Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
  • Any condition that precludes raised arms position
  • Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
  • Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF

Trial locations and contacts

167 sites in 19 countries.

167 sites in 19 countries

United States70 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131 0001

  • Texas Oncology

    Amarillo, Texas, 79124

  • Uni Of Michigan Health System

    Ann Arbor, Michigan, 48109

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Univ Of Color Anschutz Med Center

    Aurora, Colorado, 80045

  • Sidney Kimmel CCC At JH

    Baltimore, Maryland, 21231

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • University of Virginia Medical Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43221

  • Dallas VA Medical Center

    Dallas, Texas, 75216

  • Univ of Texas Southwest Med Center

    Dallas, Texas, 75390-9034

  • Rocky Mountain Cancer Centers

    Denver, Colorado, 80218

  • Duke Univ Medical Center

    Durham, North Carolina, 27710

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Hines VA Hospital

    Hines, Illinois, 60141

  • The Queens Medical Centre

    Honolulu, Hawaii, 96813

  • MD Anderson

    Houston, Texas, 77030

  • UT Health Science Center

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Mississippi Med Ctr

    Jackson, Mississippi, 39216

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Cancer Specialists of North Florida

    Jacksonville, Florida, 32256

  • University of California San Diego - Moores Cancer Center

    La Jolla, California, 92093-0658

  • VA Greater LA Healthcare System

    Los Angeles, California, 90073

  • University of California LA

    Los Angeles, California, 90095

  • University Of Miami

    Miami, Florida, 33136

  • Baptist Health South

    Miami, Florida, 33173

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Tulane Cancer Center

    New Orleans, Louisiana, 70112

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Weill Cornell Medical College

    New York, New York, 10021

  • Memorial Sloan Kettering Cancer Ctr

    New York, New York, 10065

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Urology Cancer Center PC

    Omaha, Nebraska, 68130

  • St. Joseph Hospital

    Orange, California, 92686

  • Univ Cali Irvine ALS Neuromuscular

    Orange, California, 92868

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304-1207

  • Stanford University Medical Center

    Palo Alto, California, 94304

  • Florida Cancer Affiliates

    Panama City, Florida, 32405

  • Thomas Jefferson Univ Hosp

    Philadelphia, Pennsylvania, 19107

  • Univ of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Duke Raleigh Hospital

    Raleigh, North Carolina, 27609

  • Onco Hemato Asso of SW Virginia

    Roanoke, Virginia, 24014

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Univ Of Rochester Cancer Ctr

    Rochester, New York, 14642

  • Corewell Health William Beaum Hosp

    Royal Oak, Michigan, 48073-6769

  • UT Health San Antonio Mays Cancer Center

    San Antonio, Texas, 78229

  • Sansum Clinic

    Santa Barbara, California, 93105

  • Providence Saint Johns Health Ctr

    Santa Monica, California, 90404

  • Mayo Clinic - Arizona Mayo Clinic Hospital

    Scottsdale, Arizona, 85259

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85259

  • Swedish Medical Center

    Seattle, Washington, 98122-4379

  • St Louis University

    St Louis, Missouri, 63104

  • VA St Louis Health Care System

    St Louis, Missouri, 63106

  • Wash U School of Medicine

    St Louis, Missouri, 63110

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Georgetown University-Lombardi Cancer Center

    Washington D.C., District of Columbia, 20007

  • VA Medical Center

    Washington D.C., District of Columbia, 20422

Other trials in United States

Japan17 sites

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 1138431

  • Novartis Investigative Site

    Chiba, 260-8717

  • Novartis Investigative Site

    Chuo Ku, Tokyo, 1040045

  • Novartis Investigative Site

    Fukuoka, 811-0213

  • Novartis Investigative Site

    Fukuoka, 812-0033

  • Novartis Investigative Site

    Fukuoka, 8128582

  • Novartis Investigative Site

    Fukushima, 9601295

  • Novartis Investigative Site

    Kitaadachi-gun, Saitama, 3620806

  • Novartis Investigative Site

    Kobe, Hyōgo, 6500047

  • Novartis Investigative Site

    Kumamoto, Kumamoto, 860-8556

  • Novartis Investigative Site

    Kyoto, 6068507

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 4668560

  • Novartis Investigative Site

    Okayama, 7008558

  • Novartis Investigative Site

    Sapporo, Hokkaido, 060-8648

  • Novartis Investigative Site

    Suita, Osaka, 565-0871

  • Novartis Investigative Site

    Yamagata, 990-9585

  • Novartis Investigative Site

    Yokohama, Kanagawa, 236-0004

Other trials in Japan

Spain11 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Barcelona, 08036

  • Novartis Investigative Site

    El Palmar, Murcia, 30120

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Madrid, 28046

  • Novartis Investigative Site

    Majadahonda, Madrid, 28222

  • Novartis Investigative Site

    Sabadell, Barcelona, 08208

  • Novartis Investigative Site

    Valencia, 46026

Other trials in Spain

China10 sites

  • Novartis Investigative Site

    Beijing, 100036

  • Novartis Investigative Site

    Chengdu, Sichuan, 610041

  • Novartis Investigative Site

    Guangzhou, 510060

  • Novartis Investigative Site

    Nanjing, Jiangsu, 210006

  • Novartis Investigative Site

    Nanjing, Jiangsu, 210029

  • Novartis Investigative Site

    Shanghai, 200025

  • Novartis Investigative Site

    Shanghai, 200032

  • Novartis Investigative Site

    Shanghai, 200080

  • Novartis Investigative Site

    Tianjin, 300300

  • Novartis Investigative Site

    Xian, Shanxi, 710032

Other trials in China

France10 sites

  • Novartis Investigative Site

    Bordeaux, 33075

  • Novartis Investigative Site

    Clermont-Ferrand, 63011

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Montpellier, 34298

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Paris, 75015

  • Novartis Investigative Site

    Paris, 75018

  • Novartis Investigative Site

    Strasbourg, 67000

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

  • Novartis Investigative Site

    Villejuif, 94800

Other trials in France

Canada8 sites

  • Novartis Investigative Site

    Hamilton, Ontario, L8V 5C2

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1T8

  • Novartis Investigative Site

    Montreal, Quebec, H3T 1E2

  • Novartis Investigative Site

    Montreal, Quebec, H4A 3J1

  • Novartis Investigative Site

    Québec, Quebec, G1R 2J6

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

United Kingdom8 sites

  • Novartis Investigative Site

    Belfast, BT9 7AB

  • Novartis Investigative Site

    Cambridge, CB2 0QQ

  • Novartis Investigative Site

    Glasgow, G12 0YN

  • Novartis Investigative Site

    London, EC1A 7BE

  • Novartis Investigative Site

    London, NW1 2BU

  • Novartis Investigative Site

    London, NW3 2QG

  • Novartis Investigative Site

    Middlesbrough, TS4 3BW

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Germany6 sites

  • Novartis Investigative Site

    Cologne, North Rhine-Westphalia, 50937

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    München, 80377

  • Novartis Investigative Site

    Münster, 48149

  • Novartis Investigative Site

    Rostock, 18057

  • Novartis Investigative Site

    Würzburg, Bavaria, 97080

Other trials in Germany

Netherlands4 sites

  • Novartis Investigative Site

    Delft, South Holland, 2625 AD

  • Novartis Investigative Site

    Maastricht, Limburg, 6229 HX

  • Novartis Investigative Site

    Nijmegen, Gelderland, 6500HB

  • Novartis Investigative Site

    Utrecht, 3584 CX

Other trials in Netherlands

Austria3 sites

  • Novartis Investigative Site

    Innsbruck, Tyrol, 6020

  • Novartis Investigative Site

    Linz, 4020

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Poland3 sites

  • Novartis Investigative Site

    Gliwice, Silesian Voivodeship, 44-101

  • Novartis Investigative Site

    Krakow, 30-688

  • Novartis Investigative Site

    Warsaw, 02-781

Other trials in Poland

South Korea3 sites

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 03722

  • Novartis Investigative Site

    Seoul, 05505

Other trials in South Korea

Sweden3 sites

  • Novartis Investigative Site

    Gothenburg, 413 45

  • Novartis Investigative Site

    Lund, 221 85

  • Novartis Investigative Site

    Stockholm, 17176

Other trials in Sweden

Belgium2 sites

  • Novartis Investigative Site

    Brussels, 1200

  • Novartis Investigative Site

    Ghent, 9000

Other trials in Belgium

Czechia2 sites

  • Novartis Investigative Site

    Olomouc, 779 00

  • Novartis Investigative Site

    Prague, 150 06

Other trials in Czechia

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119228

  • Novartis Investigative Site

    Singapore, 168583

Other trials in Singapore

Switzerland2 sites

  • Novartis Investigative Site

    Bern, 3010

  • Novartis Investigative Site

    Lausanne, 1011

Other trials in Switzerland

Taiwan2 sites

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Denmark1 site

  • Novartis Investigative Site

    Copenhagen, DK-2100

Other trials in Denmark

About this study

Official title: An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care (SOC), versus Standard of Care alone, in adult male patients with Metastatic hormone sensitive prostate cancer (mHSPC). In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants were enrolled in 20 countries.

Read the detailed description

In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC were to be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study was to determine whether the combination of 177Lu-PSMA-617 + SoC improved radiographic progression free survival (rPFS) over that obtained by administration of SoC alone in mHSPC patients.

The randomization was stratified according to the following three factors: disease volume (high v low), age >= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients were assessed for eligibility and were scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant was randomized via the interactive response technology (IRT) system.

Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD.

Prior treatment:

  • Up to 45 days of Luteinizing hormone releasing hormone (LHRH) agonist/antagonists was allowed prior to informed consent form (ICF) signature. If patient did not start the ADT prior randomization, ADT started as soon as possible and ideally no later than 2 weeks after randomization.
  • Up to 45 days of ARDT was allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT started as soon as possible and ideally no later than 2 weeks after randomization. Patients received ARDT as per label instructions.

Randomization period:

The participant was randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients received SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients began 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product was received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm began receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS was assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

Participants from both arms also underwent PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =< 7 days and enter the Post-treatment Follow-up.

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Being tested
177Lu-PSMA-617, 68Ga-PSMA-11, ARDT, ADT
Keywords
Lutetium-177 PSMA-617, 177Lu-PSMA-617, Androgen receptor-directed therapy, ARDT, Androgen Deprivation Therapy, ADT, Metastatic Hormone sensitive prostate cancer, mHSPC, Radiographic progression free survival, rPFS, Prostate-specific membrane antigen, PSMA, Gallium-68 PSMA-11, 68Ga-PSMA-11, Radioligand Therapy, RLT
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-PSMA-617Drug

    Also called AAA617

    administered intravenously once every 6 weeks (1 cycle) for 6 cycles

  • 68Ga-PSMA-11Drug

    Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD

  • ARDTDrug

    Administered orally on a continuous basis as per package insert and guideline

  • ADTDrug

    ADT are administered as per physician order

Study groups in NCT04720157
Study groupRoleWhat they receive
177Lu-PSMA-617ExperimentalParticipant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); Androgen receptor-directed therapy (ARDT) + Androgen deprivation therapy (ADT) is considered as SOC and treatment will be administered per the physician's order
Receives: Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-11; Drug: ARDT; Drug: ADT
Standard of CareActive comparatorFor participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order
Receives: Drug: 68Ga-PSMA-11; Drug: ARDT; Drug: ADT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic Progression Free Survival (rPFS)

    rPFS is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

    Measured: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)

Secondary outcomes (16)

  1. Overall Survival (OS) (Key Secondary Endpoint)

    OS is defined as time to death for any cause

    Measured: From date of randomization until date of death from any cause, assessed up to 50 months (estimated final OS analysis)

  2. Prostate-specific antigen 90 (PSA90) response

    PSA90 response is defined as the proportion of patients who have a more/equal 90% decrease in PSA from baseline, it will be calculated at 12, 24 and 48 months

    Measured: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)

  3. time to development of mCRPC

    Time to development of mCRPC is defined as the time from date of randomization to disease progression despite androgen deprivation therapy (ADT) presenting as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre existing disease, and/or the appearance of new metastases.

    Measured: From date of randomization till End Of Treatment (EOT) or death, which ever happen first, assessed up to 50 months (estimated final OS analysis)

  4. Progression Free Survival (PFS)

    PFS is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first

    Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)

  5. second Progression Free Survival (PFS2)

    PFS2 is defined as time from date of randomization to the first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) on next-line therapy or death from any cause, whichever occurs first.

    Measured: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)

  6. Change in nadir level of PSA lower than 0.2 ng/ml

    Proportion of patients with PSA < 0.2 ng/mL at months 12, 24 and 48 months

    Measured: From date of randomization till 30 days safety fup, whichever occur first, assessed up to 50 months (estimated final OS analysis)

  7. Time to radiographic soft tissue progression (TTSTP)

    TTSTP is defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as assessed by Blinded Independent Central Review (BICR)

    Measured: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)

  8. Time to first symptomatic skeletal event (SSE).

    Time to SSE (TTSSE) is defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first

    Measured: From date of randomization till EOT or death, whichever happens first, assessed up to 50 months (estimated final OS analysis)

  9. Overall Response Rate (ORR)

    ORR is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

    Measured: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)

  10. Disease Control Rate (DCR)

    DCR is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

    Measured: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)

  11. Duration of Response (DOR)

    DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause

    Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)

  12. Time to Response (TTR)

    TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR).

    Measured: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)

  13. Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire

    FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT-General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

    Measured: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 50 months (estimated final OS analysis)

  14. European Quality of Life ( EuroQoL) -5 Domain 5 Level Scale (EQ-5D-5L)

    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

    Measured: From screening up till 30 day safety follow-up or week 48 of long term follow up for patient prematurely discontinued, assessed up to 50 months (estimated final OS analysis)

  15. Brief Pain Inventory-short Form (PBI-SF)

    The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

    Measured: From screening up till 30 day safety follow-up or week 48 of long term follow up for patient prematurely discontinued, assessed up to 50 months (estimated final OS analysis)

  16. Number of participants with Treatment Emergent Adverse Events

    The distribution of adverse events (AE) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

    Measured: From randomization till 30 days safety follow-up, assessed up to 50 months (estimated final OS analysis)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2021
  2. Study start9 Jun 2021
  3. Primary completion13 Jan 2025
  4. Study completion11 Feb 2027 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patient randomized to SOC arm have an option to crossover to 177Lu-PSMA-617 treatment after rPFS
Masking
None (open label)
Enrolment
1,140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04720157
Sponsor's protocol ID
CAAA617C12301
Other IDs
2023-507970-42-00, 2023
Acronym
PSMAddition
Status last verified
Jun 2026
First submitted
19 Jan 2021
Last updated
8 Jun 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

Publications

  • Tagawa ST, Sartor O, Piulats JM, Saad F, Fizazi K, Reid A, Beltran H, Kramer G, Mahammedi H, Eiber M, Gupta S, Castellano D, Hauke R, Kim H, Kwak C, Pang ST, Barthelemy P, Dai D, Lee JL, Nordquist L, Szmulewitz RZ, Wiechno P, Yovine A, Smith L, Bouillaud E, Sakharova O, Morris MJ; PSMAddition Investigators. [177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. Lancet. 2026 Aug 6:S0140-6736(26)01092-5. doi: 10.1016/S0140-6736(26)01092-5. Online ahead of print.

    PubMed 42561994

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT in people with Prostatic Neoplasms, run by Novartis Pharmaceuticals at 167 sites in 19 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 22 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 167 sites in United States, Japan, Spain, China, France and 14 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic Progression Free Survival (rPFS) (time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04720157, which also lists 1 linked publication.

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 8 Jun 2026.

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