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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05983198




Registration number
NCT05983198
Ethics application status
Date submitted
24/07/2023
Date registered
9/08/2023

Titles & IDs
Public title
Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLT
Scientific title
SatisfACtion: Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With mHSPC and Heavily Pre-treated PSMA-positive mCRPC, With/Without Prior 177Lu-labelled PSMA-targeted Radioligand Therapy
Secondary ID [1] 0 0
2021-003478-30
Secondary ID [2] 0 0
CAAA802A12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 225Ac-PSMA-R2
Treatment: Other - 68Ga-PSMA-R2
Treatment: Other - 68Ga-PSMA-11

Experimental: Group-1 (mCRPC/ post-177Lu) - 1. Dose Escalation: All eligible participants with Metastatic Castration Resistant Prostate Cancer (mCRPC) who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), post-taxane based chemotherapy and heavily pre-treated and having already received prior 177Lu-labelled Prostate Specific Membrane Antigen (PSMA)-targeting Radioligand Therapy (RLT) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1.
2. Dose Expansion: Once RDE is determined for Group 1, participants who have previously received 177Lu-PSMA-RLT will be enrolled in Group 1 dose expansion.

Experimental: Group-2 (mCRPC/ pre-177Lu) - 1. Dose Escalation: All eligible participants with mCRPC who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), prior taxane-based chemotherapy is not required, but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 2.
2. Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted Radioligand Therapy (RLT) will be enrolled in Group 2 dose expansion.

Experimental: Group 3 (mHSPC/ pre-177Lu) - 1. Dose Escalation: All eligible participants with mHSPC (177Lu-labelled PSMA-targeted RLT treatment naïve), who are treatment naive or minimally treated with a) luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or bilateral orchiectomy with or without first generation antiandrogen (e.g. bicalutamide, flutamide) b) CYP17 inhibitor or ARDT exposure. Patient in this group will start treatment with 225Ac-PSMA-R2 after group 1 and group 2 patients.
2. Dose Expansion: Once RDE is determined for Group 3, participants will be enrolled in Group 3 dose expansion.


Treatment: Drugs: 225Ac-PSMA-R2
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

Treatment: Other: 68Ga-PSMA-R2
Kit for radiopharmaceutical preparation

Treatment: Other: 68Ga-PSMA-11
Kit for radiopharmaceutical preparation
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of DLTs during the DLT observation period
Assessment method [1] 0 0
To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive in: * Group-1 (mCRPC): Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu). * Group-2 (mCRPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu). * Group-3 (mHSPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).
Timepoint [1] 0 0
Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration
Primary outcome [2] 0 0
Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by group and frequency schedule
Assessment method [2] 0 0
The distribution of adverse events 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.
Timepoint [2] 0 0
From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
Primary outcome [3] 0 0
Dose Escalation: Tolerability
Assessment method [3] 0 0
Frequency of dose interruptions, reductions, discontinuations, and dose intensity by group.
Timepoint [3] 0 0
Up to 6 weeks after the first 225AC-PSMA-R2 dose administration
Primary outcome [4] 0 0
Dose Expansion: Overall Response Rate (ORR)
Assessment method [4] 0 0
Overall Response Rate (ORR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue according to Prostate Cancer Working Group 3 (PCWG3) -modified RECIST v1.1 in absence of bone progression (as per PCWG3).
Timepoint [4] 0 0
From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
Secondary outcome [1] 0 0
Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to 6 months after the last 225Ac-PSMA-R2 dose administration
Secondary outcome [2] 0 0
Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Assessed up to approximately 15 months.
Secondary outcome [3] 0 0
Dose Escalation & Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
Assessment method [3] 0 0
Tolerability of study drug will be assessed by summarizing the number of and the reasons for dose delays and dose reductions. Dose intensity will also be tabulated by treatment group.
Timepoint [3] 0 0
At day 1 of each cycle (1 cycle = up to 6 weeks)
Secondary outcome [4] 0 0
Dose Escalation: Overall Response Rate (ORR)
Assessment method [4] 0 0
Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue.
Timepoint [4] 0 0
Assessed up to approximately 15 months.
Secondary outcome [5] 0 0
Dose Escalation & Dose Expansion: Disease Control Rate (DCR)
Assessment method [5] 0 0
Disease control rate (DCR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD).
Timepoint [5] 0 0
Assessed up to approximately 15 months.
Secondary outcome [6] 0 0
Dose Escalation & Dose Expansion: Best Overall Response (BOR)
Assessment method [6] 0 0
Best Overall Response (BOR) is defined as the best response recorded from the start of the treatment until disease progression.
Timepoint [6] 0 0
Assessed up to approximately 15 months.
Secondary outcome [7] 0 0
Dose Escalation & Dose Expansion: radiographic Progression Free Survival (rPFS)
Assessment method [7] 0 0
Radiographic progression free survival (rPFS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of radiographic progression as outlined in PCWG3 modified RECIST 1.1 or death due to any cause.
Timepoint [7] 0 0
Assessed up to approximately 15 months.
Secondary outcome [8] 0 0
Dose Escalation & Dose Expansion: Overall Survival (OS)
Assessment method [8] 0 0
Overall survival (OS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of death due to any cause.
Timepoint [8] 0 0
Assessed up to approximately 15 months.
Secondary outcome [9] 0 0
Dose Escalation & Dose Expansion: Duration of Response (DoR)
Assessment method [9] 0 0
Duration of response (DOR) is defined as the time (in months) from the date of the first documented response (CR or PR) to the date of first documented progression.
Timepoint [9] 0 0
Assessed up to approximately 15 months.
Secondary outcome [10] 0 0
Dose Escalation & Dose Expansion: Time to first Symptomatic Skeletal Event (SSE)
Assessment method [10] 0 0
Time to a first symptomatic skeletal event (SSE) is defined as the time (in months) from the first administration of 225Ac-PSMA-R2 to the date of SSE or death due to any cause.
Timepoint [10] 0 0
Assessed up to approximately 15 months.
Secondary outcome [11] 0 0
Dose Escalation & Dose Expansion: Percentage of Participants with Biochemical Response by ALP and LDH
Assessment method [11] 0 0
Biochemical responses by Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) will be measured as best percentage change from baseline
Timepoint [11] 0 0
Assessed up to approximately 15 months.
Secondary outcome [12] 0 0
Dose Escalation and Dose Expansion: Percentage of Participants with Biochemical Response by PSA
Assessment method [12] 0 0
Biochemical responses as measured by Prostate Specific Antigen (PSA): PSA50 response is defined as the proportion of participants who have achieved =50% decrease from baseline at any time.
Timepoint [12] 0 0
Assessed up to approximately 15 months.
Secondary outcome [13] 0 0
Dose Escalation and Dose Expansion: Pharmacokinetics characterization of 225Ac-PSMA-R2
Assessment method [13] 0 0
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization.
Timepoint [13] 0 0
At Cycle (C) 1 Day (D) 1 at different measurement times, and one timepoint at C1 D2, C1 D3 and C1 D4
Secondary outcome [14] 0 0
Dose escalation and dose expansion: To assess the impact of 225Ac-PSMA-R2 on participant reported outcomes
Assessment method [14] 0 0
Change in heath related quality of life.
Timepoint [14] 0 0
From baseline until 24 months after the end of treatment

Eligibility
Key inclusion criteria
Key

* Evidence of PSMA-positive disease by 68Ga-PSMA-11 PET/CT and eligible as determined by central reading
* Documented progressive mCRPC or mHSPC
* Adequate organ function
* Prior orchiectomy or ongoing ADT and should have received prior 177Lu-PSMA-RLT (Group1 dose escalation & expansion) or never received 177Lu-PSMA-RLT (Group 2 and Group 3 dose escalation & expansion).

Key
Minimum age
18 Years
Maximum age
100 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Any other investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy
* Any systemic anti-cancer therapy within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy
* Uncontrolled pain or incompatibility that may result in participant's lack of ability to comply with imaging procedures
* History of CNS metastases and symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
* History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months prior to ICF signature and/or clinically active significant cardiac disease
* Diagnosis of other malignancies in the past three years expected to alter life expectancy or may interfere with disease assessment

Other protocol-defined inclusion/exclusion criteria may apply.

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



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/11/2029
Actual
Sample size
Target
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Quebec
Country [2] 0 0
France
State/province [2] 0 0
Cote D Or
Country [3] 0 0
France
State/province [3] 0 0
Clermont-Ferrand
Country [4] 0 0
France
State/province [4] 0 0
Lyon
Country [5] 0 0
France
State/province [5] 0 0
Nantes Cedex 1
Country [6] 0 0
France
State/province [6] 0 0
Saint Herblain
Country [7] 0 0
France
State/province [7] 0 0
Vandoeuvre Les Nancy

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05983198