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Trial registered on ANZCTR


Registration number
ACTRN12622001378718
Ethics application status
Approved
Date submitted
27/09/2022
Date registered
26/10/2022
Date last updated
2/11/2023
Date data sharing statement initially provided
26/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
An early phase clinical trial to measure the safe dose of a new alpha-radiopharmaceutical for the treatment of advanced prostate cancer
Scientific title
Phase I/IIa Dose Escalation and Toxicity Study of [212Pb]Pb-ADVC001 in Metastatic Prostate Adenocarcinoma (TheraPb – Phase I/II)
Secondary ID [1] 306921 0
none
Universal Trial Number (UTN)
Trial acronym
TheraPb-phase I/II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Prostate Cancer 326029 0
Condition category
Condition code
Cancer 323336 323336 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment with a novel therapeutic ADVC001 complexed with 212-Pb (an alpha emitting radio-isotope). Patients with metastatic prostate adenocarcinoma are treated around every six weeks (for four cycles in total). There is no control group.

The starting dose is 60MBq. We are not dosing per kg; as is normal clinically in this patient group in Australia.

The cohorts will be escalated: 60 / 90 / 120/ 150 MBq

We intend 4 cohorts of three patients
All treatment is given by intravenous infusion

The frequency is intended to be 6 weekly but it can be +/- 2 weeks
At the completion of each cohort the data will be reviewed by the Safety Review Committee (SRC) and only if we have not reached a dose limiting toxicity (DLT) will the next cohort be enrolled. Under the 3+3 design if 2 of the 3 patients develop a DLT we will recruit 3 further patients at that dose level. A waiting period of 56 days will occur between cohorts. Within the cohort we will delay the patient (for a haematological DLT) and/or reduce dose at investigator discretion. The cohort will be treated (for cycle 1 and then 56 days after administration of the last patient in the dose escalation cohort (of three patients); the next cohort can be enrolled assuming the SRC are happy with the next cohort going ahead.

The radiopharmaceutical dose undergoes extensive quality assurance (QA) prior to administration so we know the exact activity injected; and this is a time critical dose. The time of the infusion will be recorded. Patient measurements will be taken at cycle one (C1) over the next 12 hours until it is safe to discharge.
Intervention code [1] 323368 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331071 0
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), assessed in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Timepoint [1] 331071 0
Up to Week 36 after starting treatment
Primary outcome [2] 331072 0
Incidence and severity of dose-limiting toxicities, assessed in accordance with NCI CTCAE V5.
Timepoint [2] 331072 0
Up to Week 6 after starting treatment
Primary outcome [3] 336469 0
Frequency of clinically significant changes from baseline in clinical chemistry and hematology blood laboratory values.
Timepoint [3] 336469 0
Primary outcome [4] 336470 0
Frequency of clinically significant changes from baseline in clinical chemistry and hematology blood laboratory values.
Timepoint [4] 336470 0
Up to Week 36 after starting treatment
Secondary outcome [1] 408618 0
Whole body biodistribution and organ radiation dosimetry of [212Pb]Pb-ADVC001 from dosimetry scans
Timepoint [1] 408618 0
Up to Week 19 after starting treatment
Secondary outcome [2] 408619 0
Comparability of biodistribution of [212Pb]Pb-ADVC001 to PSMA targeting positron emission tomography (PET) imaging agents
Timepoint [2] 408619 0
Up to Week 19 after starting treatment
Secondary outcome [3] 408620 0
Therapeutic efficacy assessed by radiographic progression free survival (rPFS), objective response rate and prostate specific antigen (PSA) response.
Timepoint [3] 408620 0
Up to Week 36 after starting treatment
Secondary outcome [4] 408621 0
Change from baseline in serum alkaline phosphatase (ALP) values
Timepoint [4] 408621 0
Up to Week 36 after starting treatment

Eligibility
Key inclusion criteria
• Male aged 18 years or older with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma or metastatic disease typical of prostate cancer (i.e. Involving bone or pelvic lymph nodes or para-aortic lymph nodes)
• Patients with castration-resistant prostate cancer that have received at least one cycle of androgen receptor therapy and exposure to a taxane-based chemotherapy unless considered contraindicated by a medical oncologist or patient declines treatment
• Progressive disease with rising PSA level, or new lesion(s) in the viscera or lymph nodes as per RECIST 1.1 or in bone as per Prostate Cancer Working Group 3
• Significant PSMA avidity on [68Ga]Ga-PSMA PET/CT
• ECOG Performance status 0 to 2
• Adequate renal, bone and liver function (Absolute neutrophil count: greater than or equal to 2 x 109 /L , Hemoglobin: greater than or equal to 90 g/L, Platelet count: greater than or equal to 150,000 x 109/L, Serum creatinine: less than 1.5 x upper limit of normal (ULN) i.e = 125 umol/L or calculated creatinine clearance greater than or equal to 60 mL/min/1.73 m2 by Cockcroft-Gault formula, Serum total bilirubin: less than 1.5 x ULN (unless the patient has Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: less than 1.5 x ULN in the absence of liver metastases; less than 3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
• Estimated life expectancy greater than 12 weeks
• Willing and able to comply with all study requirements, including the timing and nature of all required assessments (i.e. blood testing and scanning.)
• Have provided written Informed Consent for participation in this trial
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Prostate cancer with known significant sarcomatoid or spindle cell or neuroendocrine small cell components
• Sjogren’s syndrome
• ECOG status >2
• Prior treatment with radioligand therapy
• Contraindications to the use of corticosteroid treatment
• Active malignancy other than prostate cancer (excluding non-melanomatous skin cancers)
• Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
• Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule
• Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
• Severe claustrophobia that may impact the participants ability to comply with all aspects of the imaging protocol

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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
RECIST reporting will be used for the trial. PSMA PET scanning will be done at two points and PSA will be measured in serum. The imaging will be reported by the independent imaging core lab.
A direct comparison will be undertaken between the scans at baseline and the assessment points one and two. The RECIST reports will be compared and the paired PSA measurements will be compared using descriptive statistics and a students T-test. The number of subjects arises from the study design and is intended to include enough patients to quantify toxicity but at the same time not to expose large numbers of patients until the dose is better defined.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
1/11/2023
Date of last participant enrolment
Anticipated
28/06/2024
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
18
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 22197 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 25802 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 37350 0
4029 - Herston
Recruitment postcode(s) [2] 37351 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [3] 41627 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 311241 0
Commercial sector/Industry
Name [1] 311241 0
AdvanCell Isotopes Pty Ltd
Country [1] 311241 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AdvanCell Isotopes Pty Ltd
Address
L 7, 167 Macquarie St,
Sydney. NSW 2000
Country
Australia
Secondary sponsor category [1] 312599 0
None
Name [1] 312599 0
Address [1] 312599 0
Country [1] 312599 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310754 0
Royal Brisbane and Women's Hospital Ethics Committee HREC A
Ethics committee address [1] 310754 0
Ethics committee country [1] 310754 0
Australia
Date submitted for ethics approval [1] 310754 0
09/08/2022
Approval date [1] 310754 0
22/11/2022
Ethics approval number [1] 310754 0
Project ID: 87743

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

Contacts
Principal investigator
Name 118750 0
A/Prof David Wyld
Address 118750 0
Department of Medical Oncology,
Royal Brisbane and Women's Hospital,
Cnr Butterfield St and Bowen Bridge Rd,
Herston,
Brisbane QLD 4029
Country 118750 0
Australia
Phone 118750 0
+61 7 3646 8111
Fax 118750 0
Email 118750 0
David.Wyld@health.qld.gov.au
Contact person for public queries
Name 118751 0
Stephen Rose
Address 118751 0
Head of Clinical Development, AdvanCell Isotopes Pty Ltd, Level 7, Macquarie House, 167 Macquarie Street, Sydney, NSW, 2000, Australia.
Country 118751 0
Australia
Phone 118751 0
+61 498 322 488
Fax 118751 0
+61 2 8000 4198
Email 118751 0
contact@advancell.com.au
Contact person for scientific queries
Name 118752 0
Stephen Rose
Address 118752 0
Head of Clinical Development, AdvanCell Isotopes Pty Ltd, Level 7, Macquarie House, 167 Macquarie Street, Sydney, NSW, 2000, Australia.
Country 118752 0
Australia
Phone 118752 0
+61 498 322 488
Fax 118752 0
+61 (2) 8000 4198
Email 118752 0
contact@advanCell.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Large amounts of imaging data and no agreed format for sharing


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16554Ethical approval  contact@advanCell.com.au


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16554[Marked for deletion] Ethical approval  contact@advanCell.com.au

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.