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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
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
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
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)
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)
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)
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.
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)
Timepoint [4] 0 0
Assessed up to approximately 15 months.
Secondary outcome [5] 0 0
Dose Escalation & Dose Expansion: Disease Control Rate (DCR)
Timepoint [5] 0 0
Assessed up to approximately 15 months.
Secondary outcome [6] 0 0
Dose Escalation & Dose Expansion: Best Overall Response (BOR)
Timepoint [6] 0 0
Assessed up to approximately 15 months.
Secondary outcome [7] 0 0
Dose Escalation & Dose Expansion: radiographic Progression Free Survival (rPFS)
Timepoint [7] 0 0
Assessed up to approximately 15 months.
Secondary outcome [8] 0 0
Dose Escalation & Dose Expansion: Overall Survival (OS)
Timepoint [8] 0 0
Assessed up to approximately 15 months.
Secondary outcome [9] 0 0
Dose Escalation & Dose Expansion: Duration of Response (DoR)
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)
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
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
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
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
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
No limit
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
15/12/2027
Actual
Sample size
Target
200
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
France
State/province [1] 0 0
Cote D Or
Country [2] 0 0
France
State/province [2] 0 0
Clermont-Ferrand
Country [3] 0 0
France
State/province [3] 0 0
Lyon
Country [4] 0 0
France
State/province [4] 0 0
Nantes Cedex 1
Country [5] 0 0
France
State/province [5] 0 0
Saint Herblain
Country [6] 0 0
France
State/province [6] 0 0
Vandoeuvre Les Nancy

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

Ethics approval
Ethics application status

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

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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