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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT05720130
Ethics application status
Date submitted
7/01/2023
Date registered
9/02/2023
Date last updated
31/07/2024

Titles & IDs
Public title
Phase Ib/IIa Dose Escalation and Expansion Study of [²¹²Pb]Pb-ADVC001 in Metastatic Castration Resistant Prostate Cancer (TheraPb - Phase I/II Study).
Scientific title
Phase Ib/IIa Dose Escalation and Expansion Study of [²¹²Pb]Pb-ADVC001 in Metastatic Castration Resistant Prostate Cancer (TheraPb - Phase I/II Study).
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:
Prostate Cancer 0 0
Metastatic Castration-resistant 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 - [²¹²Pb]Pb-ADVC001

Experimental: mCRPC - Phase 1b Dose Escalation:

Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi and taxane-based chemotherapy at any time in the course of their disease.

Phase 2a Dose Expansion:

Group 1: Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi at any time in the course of their disease and received taxane-based chemotherapy for the treatment of mCRPC.

Group 2: Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi at any time in the course of their disease and has not received a taxane for the treatment of mCRPC.

Group 3: Participants with PSMA-positive mCRPC who have had exposure to ¹77Lu-PSMA at any time in the course of their disease.


Treatment: Drugs: [²¹²Pb]Pb-ADVC001
Ph1b Escalation

Drug: \[²¹²Pb\]Pb-ADVC001administered intravenously per dose escalation scheme

Dose Level 1

- 60 MBq, 4 cycles every 6 weeks

Dose Level 2a

- 120 MBq, 4 to 6 cycles every 4 weeks

Dose Level 2b

- Optional cohort of 120 MBq, 4 to 6 cycles every 2 weeks

Dose Level 3a

- 160 MBq, 4 to 6 cycles every 4 weeks

Dose Level 3b

- Optional cohort of 160 MBq, 4 to 6 cycles every 2 weeks

Dose Level 4a

- 200 MBq, 4 to 6 cycles every 4 weeks

Dose Level 4b

- Optional cohort of 200 MBq, 4 to 6 cycles every 2 weeks

Ph2a Expansion

Drug: \[²¹²Pb\]Pb-ADVC001 at recommended phase 2 dose and schedule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
RP2D
Timepoint [1] 0 0
Up to 37 Months
Secondary outcome [1] 0 0
Maximum tolerated dose (MTD)
Timepoint [1] 0 0
Up to 37 months
Secondary outcome [2] 0 0
Safety and Tolerability
Timepoint [2] 0 0
Up to 37 months
Secondary outcome [3] 0 0
Dosimetry
Timepoint [3] 0 0
From first dose of study drug through end of treatment
Secondary outcome [4] 0 0
Preliminary therapeutic efficacy
Timepoint [4] 0 0
Up to 37 months

Eligibility
Key inclusion criteria
* Be willing and able to provide written informed consent for the trial.
* Adults aged 18 years or older at the time of consent.
* Has documented metastatic adenocarcinoma of the prostate, confirmed by histopathology.
* Has metastatic disease (= 1 metastatic lesion present on baseline CT, magnetic resonance imaging [MRI] or bone scintigraphy scan).
* Has castration-resistant prostate cancer progressing or has progressed on androgen receptor therapy and must have castrate level of serum/plasma testosterone (= 50 ng/dL or = 1.7 nmol/L).
* Has disease that is progressing at Screening, despite a castrate testosterone level (= 50 ng/dL or = 1.7 nmol/L), by the demonstration of at least one of the following:

1. Increase in PSA greater than 25% and > 2 ng/mL above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart
2. Progressive disease or new lesion(s) (relative to previous imaging) in the viscera or lymph nodes as per the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or in bone as per Prostate Cancer Working Group 3 (PCWG3). Any ambiguous results are to be confirmed by additional imaging modality (e.g., CT or MRI, Tc 99m bone scintigraphy).
* a. For Phase 1b Dose Escalation: Exposure to at least one ARPi and taxane-based chemotherapy at any time in the course of their disease (unless taxanes considered contraindicated or declined by participant).

b. For Phase 2a Expansion Group 1: Exposure to at least one ARPi at any time in the course of their disease and received taxane-based chemotherapy for the treatment of mCRPC.

c. For Phase 2a Expansion Group 2: Has had exposure to at least one ARPi at any time in the course of their disease and has not received a taxane for the treatment of mCRPC. Participants may have received a taxane-based therapy in the (neo)adjuvant or mHSPC setting at least 12 months prior to first treatment cycle (C1D1).

d. For Phase 2a Expansion Group 3: Has had exposure to ¹77Lu-PSMA at any time in the course of their disease.
* Has disease that is prostate specific membrane antigen (PSMA) positive, as demonstrated by 68Ga-PSMA-PET/CT or ¹8F-based PSMA PET/CT and confirmed as eligible by local reader. PSMA-positive participants are defined as those having at least one tumor lesion with 68Ga- or ¹8F- PSMA PET CT uptake greater than normal liver (based on visual assessment) and all tumor lesions larger than size criteria with 68Ga- or ¹8F-PSMA uptake greater than liver [short axis size criteria: organs = 1 cm, lymph nodes = 2.5 cm, bones (soft tissue component) = 1 cm].
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
* Has adequate renal, haematological, and liver function, as defined by the following safety laboratory results at Screening
* Estimated life expectancy > 6 months.
* Has the capacity to understand the study and be willing and able to comply with all study requirements, including the timing and nature of all required assessments.
* Must agree to comply with the radiation protection guidelines (including hospital admissions and isolation, where relevant) that are applied by the treating institution.
* Must agree to practice adequate precautions to prevent pregnancy in a partner to avoid potential problems associated with radiation exposure to the unborn child.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Has prostate cancer with known significant sarcomatoid or spindle cell or neuroendocrine small cell components, as determined by the Investigator. Participants with minor sarcomatoid, spindle cell or neuroendocrine small cell prostate cancer, but otherwise PSMA-expressing disease, may be eligible at the discretion of the Investigator.
* Has symptomatic dry eye, symptomatic dry mouth, Sjogren's syndrome or other pathologies affecting salivary gland function.
* Has received prior treatment with radiopharmaceuticals containing the following radioisotopes: lutetium-177, actinium-225, strontium-89, samarium-153, rhenium-186, rhenium-188, or other lead-212-containing radiopharmaceuticals. Note: prior radium-223 exposure is not exclusionary, and prior exposure to ¹77Lu-PSMA is not exclusionary for Group 3 participants in Phase 2a Expansion, provided treatment ceased at least 12 weeks prior to first treatment cycle (C1D1).
* Has received systemic anti-cancer therapy other than ADT and ARPi (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within four weeks of first study cycle. Participants will not be eligible if any significant adverse events related to prior systemic anti-cancer therapy have not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) = Grade 2 at the time of Screening, even if the systemic therapy ceased greater than four weeks prior to first treatment cycle (C1D1).
* Has received any investigational agent within four weeks of first treatment cycle (C1D1).
* Has concurrent other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease-free for more than three years are eligible, as are participants with adequately treated non-melanoma skin cancer, and those with non-muscle invasive bladder cancer.
* Has known brain metastases of any size or has a single hepatic metastasis > 1 cm (longest diameter), or more than one hepatic metastases of any size.
* Has symptoms of spinal cord compression or impending spinal cord compression.
* Has diffuse bone-marrow involvement, i.e. "superscan", defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues, along with absent or faint activity in the genitourinary tract due to diffuse bone/bone marrow metastases).
* Has a serious active or sub-clinical infection, or angina pectoris, or heart failure (New York Heart Association [NYHA] Class III or IV), or significantly prolonged QT interval, or other serious illness involving the cardiac, respiratory, central nervous system, renal, hepatic or haematological organ systems, which might impair the ability to participate in this study to the full extent, or which may require treatment that could interact with study treatment. Note: participants with renal obstruction of any degree may be eligible to participate at the discretion of the Investigator.
* Evidence of untreated urinary tract obstruction (e.g., hydroureter or hydronephrosis). Participants who undergo a successful decompressive procedure prior to treatment will not be excluded. Note: participants with renal obstruction of any degree may be eligible to participate at the discretion of the Investigator.
* Has a 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.
* Has severe claustrophobia or other condition (e.g., pain) that may impact the ability to comply with the imaging aspects of this protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
15/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
100
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 prospective, open-label, non-randomised, dose-escalation and expansion study. The study aims to determine the safety and tolerability of escalating doses of \[²¹²Pb\]Pb-ADVC001 administered every 4 or every 2 weeks during the dose finding phase (Phase 1b), and then aims to assess the efficacy and safety of \[²¹²Pb\]Pb-ADVC001 at the RP2D in 3 participant groups in the expansion phase (Phase 2a).
Trial website
https://clinicaltrials.gov/study/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
[email protected]
Contact person for scientific queries



Summary Results

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