Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05720130




Registration number
NCT05720130
Ethics application status
Date submitted
7/01/2023
Date registered
9/02/2023
Date last updated
3/11/2023

Titles & IDs
Public title
Dose Escalation and Efficacy Study of 212Pb-ADVC001 in Patients With Metastatic Castration Resistant Prostate Cancer.
Scientific title
TheraPb: Phase I/IIa Dose Escalation and Toxicity Study of [212Pb]Pb-ADVC001 in Metastatic Prostate Adenocarcinoma
Secondary ID [1] 0 0
TheraPb-ADVC001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [212Pb]Pb-ADVC001

Experimental: [212Pb]Pb-ADVC001 - There is only a single treatment arm. Participants with metastatic Castration Resistant Prostate Cancer that have received prior Androgen Receptor Pathway Inhibitors (e.g., Abiraterone, Enzalutamide) and chemotherapy (or can have declined chemotherapy), who have not been previously treated with [177Lu]Lu-PSMA radioligand therapy. Four cohorts will receive escalating doses of 60 MBq, 90 MBq, 120MBq and 150MBq of [212Pb]Pb-ADVC001. Participants will receive a dose via intravenous injection every 6 weeks (+/- 2 weeks) for no more than 4 cycles.


Treatment: Drugs: [212Pb]Pb-ADVC001
[212Pb]Pb-ADVC001 administered intravenously under the dose escalation schedule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 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] 0 0
Up to Week 36
Primary outcome [2] 0 0
Incidence and severity of dose-limiting toxicities, assessed in accordance with NCI CTCAE V5.
Timepoint [2] 0 0
Up to Week 6
Primary outcome [3] 0 0
Frequency of clinically significant changes from baseline in clinical chemistry and hematology laboratory values.
Timepoint [3] 0 0
Up to Week 36
Primary outcome [4] 0 0
Maximum tolerated dose (MTD) of [212Pb]Pb-ADVC001, assessed using the standard 3+3 dose escalation design.
Timepoint [4] 0 0
Up to 6 weeks
Primary outcome [5] 0 0
Recommended Phase 2 Dose (RP2D) for [212Pb]Pb-ADVC001.
Timepoint [5] 0 0
Through study completion, estimated 12 months study duration.
Secondary outcome [1] 0 0
Whole body biodistribution and organ radiation dosimetry of [212Pb]Pb-ADVC001
Timepoint [1] 0 0
Up to Week 19
Secondary outcome [2] 0 0
Whole body biodistribution and organ radiation dosimetry of [212Pb]Pb-ADVC001
Timepoint [2] 0 0
Up to Week 19
Secondary outcome [3] 0 0
Comparability of biodistribution of [212Pb]Pb-ADVC001 to PSMA targeting positron emission tomography (PET) imaging agents
Timepoint [3] 0 0
Up to Week 19
Secondary outcome [4] 0 0
Radiographic progression free survival (rPFS)
Timepoint [4] 0 0
Up to Week 25
Secondary outcome [5] 0 0
Objective response rate
Timepoint [5] 0 0
Up to Week 25
Secondary outcome [6] 0 0
Prostate specific antigen (PSA) response
Timepoint [6] 0 0
Up to Week 36
Secondary outcome [7] 0 0
Change from baseline in serum alkaline phosphatase (ALP) values.
Timepoint [7] 0 0
Up to Week 36

Eligibility
Key inclusion criteria
- Male and 18 years of age or older at the time of signing the consent form with
metastatic adenocarcinoma of the prostate, confirmed by histopathology.

- Castration-resistant prostate cancer progressing or has progressed on androgen
receptor therapy.

- Had exposure to a taxane-based chemotherapy at any time in the course of their
disease, unless contraindicated or declined.

• 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-PSMA PET/CT or 18F-based PSMA PET/CT (at least one
site of disease with maximum standardised uptake value (SUVmax) = 1.5 times the SUV of
normal liver).

- Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2.

- Adequate renal, bone and liver function (Absolute neutrophil count: =2 x 10^9/L ,
Hemoglobin: =90 g/L, Platelet count: >150,000 x 10^9/L, Serum creatinine: <1.5 x upper
limit of normal (ULN) i.e = 125 umol/L or calculated creatinine clearance = 60
mL/min/1.73 m2 by Cockcroft-Gault formula, Serum total bilirubin: <1.5 x ULN (unless
the patient has Gilbert's syndrome in which case direct bilirubin must be normal),
Serum aspartate aminotransferase (AST) and alanine transaminase (ALT): <1.5 x ULN in
the absence of liver metastases; <3 x ULN if due to liver metastases (in both
circumstances bilirubin must meet entry criteria).

- Estimated life expectancy >12 weeks

- Willing and able to comply with all study requirements, including the timing and
nature of all required assessments.

- Agree to practice adequate precautions to prevent pregnancy in a partner.
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 or other pathologies affecting salivary gland function.

- Prior treatment with radiopharmaceuticals containing the following radioisotopes:
lutetium-177, actinium-225, strontium-89, samarium-153, rhenium-186, rhenium-188,
radium-223 or other lead-212-containing radiopharmaceuticals.

- Received systemic anti-cancer therapy and/or radiation therapy within four weeks of
Screening.

- Received any investigational agent within four weeks of Screening.

- Contraindications to the use of corticosteroid treatment.

- Concurrent other malignancies that are expected to alter life expectancy or may
interfere with disease assessment.

- Known brain metastases of any size or hepatic metastases > 1 cm (longest diameter).

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

- Known alteration in breast cancer genes (BRCA) BRCA1, BRCA2 or Ataxia Telangiectasia
Mutated Gene (ATM), and are eligible to receive Olaparib therapy according to their
treating institution standard of care.

- 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
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
Other
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
15/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2024
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
4102 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AdvanCell Isotopes Pty Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human, dose escalation and efficacy study of [212Pb]Pb-ADVC001 in
participants with PSMA-positive metastatic Castration Resistant Prostate Cancer (mCRPC).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05720130
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Wyld
Address 0 0
Royal Brisbane & Women's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AdvanCell Isotopes Pty Limited
Address 0 0
Country 0 0
Phone 0 0
612 8000 4199
Fax 0 0
Email 0 0
contact@advancell.com.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05720130