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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05383079




Registration number
NCT05383079
Ethics application status
Date submitted
16/05/2022
Date registered
19/05/2022
Date last updated
27/10/2023

Titles & IDs
Public title
Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men With Metastatic Castration-Resistant Prostate Cancer
Scientific title
Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men With Metastatic Castration-Resistant Prostate Cancer
Secondary ID [1] 0 0
21/029
Universal Trial Number (UTN)
Trial acronym
AlphaBet
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer 0 0
mCRPC 0 0
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 - Lutetium-177 PSMA-I&T
Treatment: Drugs - Radium-223

Experimental: Radium-223 and Lutetium-177 PSMA-I&T - In this single-arm study, patients will receive 7.4 GBq of 177Lu-PSMA-I&T on Day 1 of every 6 week Cycle. Radium-223 will be administered concurrently every 6 weeks. The dose of Radium-223 will vary in dose-escalation. Up to 6 Cycles will be given.


Treatment: Drugs: Lutetium-177 PSMA-I&T
Patients will be given 7.4 GBq of 177Lu-PSMA every 6 weeks for up to 6 Cycles

Treatment: Drugs: Radium-223
During dose escalation, doses of Radium-223 that will be administered include 27.5 kBq/kg and 55 kBq/kg. The maximum tolerated dose of Radium-223 will be used during dose expansion. Radium-223 will be given once every 6 weeks for up to 6 doses between day 1-5 of each Cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting toxicities (DLTs)
Timepoint [1] 0 0
Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
Primary outcome [2] 0 0
Maximum Tolerated dose (MTD)
Timepoint [2] 0 0
Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [3] 0 0
Up to 30 months from the time the first patient is recruited.
Primary outcome [4] 0 0
50% Prostate-Specific Antigen Response Rate (PSA-RR)
Timepoint [4] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [1] 0 0
Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Timepoint [1] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [2] 0 0
Radiographic Progression-Free Survival (rPFS)
Timepoint [2] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [3] 0 0
PSA progression free survival (PSA-PFS)
Timepoint [3] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [5] 0 0
Objective response rate (ORR) by RECIST1.1 in patients with measurable disease
Timepoint [5] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [6] 0 0
Progression Free Survival (PFS)
Timepoint [6] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [7] 0 0
Describe pain within 12 months of treatment commencement
Timepoint [7] 0 0
Through completion of 12 months after treatment commencement of last patient
Secondary outcome [8] 0 0
Describe health-related QoL within 12 months of treatment commencement
Timepoint [8] 0 0
Through completion of 12 months after treatment commencement of last patient

Eligibility
Key inclusion criteria
- Patient must be = 18 years of age and must have provided written informed consent.

- Histologically or cytologically confirmed adenocarcinoma of the prostate, OR
unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic
lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.

- Eastern Cooperative Oncology Group (ECOG) performance status of = 2

- Patients must have progressed on = 1 second-generation AR-targeted agent (e.g.,
enzalutamide, abiraterone, apalutamide, or darolutamide).

- Patients must have progressive disease for study entry. PCWG3 defines this as any one
of the following:

- PSA progression: minimum of two rising PSA values from a baseline measurement
with an interval of = 1 week between each measurement.

- Soft tissue progression as per RECIST 1.1 criteria

- Bone progression: = 2 new lesions on bone scan

- Symptomatic progression eg. Bone pain

- At least three weeks since receiving anti-cancer treatment (other than ADT), the
completion of surgery or radiotherapy prior to registration.

- Prior surgical orchiectomy or chemical castration maintained on luteinizing
hormone-releasing hormone (LHRH) analogue (agonist or antagonist).

- Serum testosterone levels = 1.75nmol/L (= 50ng/dL) within 28 days before registration.

- Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a
site of disease, and SUVmax >10 at sites of measurable disease >10mm (unless subject
to factors explaining a lower uptake, e.g. respiratory motion, reconstruction
artefact).

- = 2 bone metastases must be present on bone scintigraphy which have not been
previously treated with radiotherapy.

- No contraindication to treatment with a bone antiresorptive agent such as denosumab or
zoledronic acid.

- Patients must have adequate bone marrow, hepatic and renal function documented within
28 days prior to registration, defined as:

- Haemoglobin = 90 g/L independent of transfusions (no red blood cell transfusion
in last four weeks)

- Absolute neutrophil count = 1.5x10^9/L

- Platelets = 150 x10^9/L

- Total bilirubin = 1.5 x upper limit of normal (ULN) except for patients with
known Gilbert's syndrome, where this applies for the unconjugated bilirubin
component.

- Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN if there
is no evidence of liver metastasis or = 5 x ULN in the presence of liver
metastases

- Albumin = 25 g/L

- Adequate renal function: patients must have a creatinine clearance estimated of =
40 mL/min using the Cockcroft Gault equation

- Sexually active patients are willing to use medically acceptable forms of barrier
contraception.

- Willing to undergo biopsies, if disease is considered accessible and biopsy is
feasible.

- Willing and able to comply with all study requirements, including all treatments and
the timing and nature of all required assessments.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry:

- Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT

- Prior treatment with 223Ra or 177Lu-PSMA.

- Has received more than one previous line of chemotherapy for the treatment of
metastatic prostate cancer.

- Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no
uptake on WBBS (for bone metastases).

- Other malignancies within the previous 2 years other than basal cell or squamous cell
carcinomas of skin or other cancers that are unlikely to recur within 24 months.

- Symptomatic brain metastases or leptomeningeal metastases.

- Patients with symptomatic or impending cord compression unless appropriately treated
beforehand and clinically stable for = four weeks.

- Concurrent illness, including severe infection that may jeopardise the ability of the
patient to undergo the procedures outlined in this protocol with reasonable safety.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 1/Phase 2
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
13/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This clinical trial will evaluate the safety of Radium-223 in combination with 177Lu-PSMA-I&T
in metastatic castration-resistant prostate cancer: Phase I/II study
Trial website
https://clinicaltrials.gov/ct2/show/NCT05383079
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Prof Michael Hofman
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gaurav Sharma
Address 0 0
Country 0 0
Phone 0 0
03 85596830
Fax 0 0
Email 0 0
Gaurav.Sharma@petermac.org
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05383079