Dose Escalation and Efficacy Study of 212Pb-ADVC001 in Patients With Metastatic Castration Resistant Prostate Cancer.

Prostatic Neoplasms Clinical Trial

Official title:

TheraPb: Phase I/IIa Dose Escalation and Toxicity Study of [212Pb]Pb-ADVC001 in Metastatic Prostate Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05720130
• Other study ID #: TheraPb-ADVC001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 15, 2023
• Est. completion date: June 2024

Study information

• Verified date: November 2023
• Source: AdvanCell Isotopes Pty Limited
• Contact: AdvanCell Isotopes Pty Limited
• Phone: 612 8000 4199
• Email: contact[@]advancell.com.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This is a single arm, non-randomized, toxicity and dose finding study. The trial will include a maximum of 18 patients with confirmed mCRPC and no prior history of radioligand therapy. The study is based on a 3 + 3 design with 4 cohorts of patients receiving escalating doses 60, 90, 120 and 150MBq of [212Pb]Pb-ADVC001. Each patient in each cohort will be given the same dose and a maximum of 4 cycles of therapy administered at 6 weekly intervals. The decision to recruit the next cohort of patients and escalate the dose will be made after reviewing all safety data from the previous cohort acquired over 6 weeks after the first cycle of therapy. In this manner, recruitment of the next cohort can occur before all treatment cycles have been administered to the previous cohort.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Castration-Resistant
• Prostatic Neoplasms

Intervention

Drug:
• [212Pb]Pb-ADVC001
[212Pb]Pb-ADVC001 administered intravenously under the dose escalation schedule

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane & Women's Hospital	Brisbane	Queensland

Sponsors (1)

Lead Sponsor	Collaborator
AdvanCell Isotopes Pty Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumour response assessed using [68Ga]Ga- or [18F]F-based PSMA PET/CT	Tumour response assessed using [68Ga]Ga- or [18F]F-based PSMA PET imaging, based on the Consensus Statement on PSMA PET Response Assessment Criteria in Prostate Cancer.	Up to Week 25
Primary	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.		Up to Week 36
Primary	Incidence and severity of dose-limiting toxicities, assessed in accordance with NCI CTCAE V5.		Up to Week 6
Primary	Frequency of clinically significant changes from baseline in clinical chemistry and hematology laboratory values.		Up to Week 36
Primary	Maximum tolerated dose (MTD) of [212Pb]Pb-ADVC001, assessed using the standard 3+3 dose escalation design.		Up to 6 weeks
Primary	Recommended Phase 2 Dose (RP2D) for [212Pb]Pb-ADVC001.	The RP2D is defined as the dose level that is well tolerated in patients. This will be equal or less than the MTD. In the case where an MTD is not identified, even at the highest dose level tested, the RP2D may be determined based on data indicating adequate tolerability and therapeutic effectiveness.	Through study completion, estimated 12 months study duration.
Secondary	Whole body biodistribution and organ radiation dosimetry of [212Pb]Pb-ADVC001	Absorbed radiation doses to kidneys, liver, lungs, spleen, and salivary glands.	Up to Week 19
Secondary	Whole body biodistribution and organ radiation dosimetry of [212Pb]Pb-ADVC001	Favourable and selective uptake of [212Pb]Pb-ADVC001 in PSMA-expressing tumours as determined by qualitative image read by expert radiologist or nuclear medicine physician, and, where possible, tumour-to-healthy tissue ratios.	Up to Week 19
Secondary	Comparability of biodistribution of [212Pb]Pb-ADVC001 to PSMA targeting positron emission tomography (PET) imaging agents	Biodistribution of [212Pb]Pb-ADVC001 and 68Ga-PSMA (or 18F based-PSMA), as determined by image interpretation by expert radiologist or nuclear medicine physician.	Up to Week 19
Secondary	Radiographic progression free survival (rPFS)	rPFS defined as the time from enrolment to the occurrence of one of the following: Progression of measurable lesions using RECIST 1.1; Progression of bone lesions using PCWG3 criteria; Death due to any cause;	Up to Week 25
Secondary	Objective response rate	Objective response rate in patients with measurable disease (RECIST 1.1).	Up to Week 25
Secondary	Prostate specific antigen (PSA) response	PSA response defined as a reduction from baseline PSA level of at least 50%, maintained for at least 3 weeks.	Up to Week 36
Secondary	Change from baseline in serum alkaline phosphatase (ALP) values.		Up to Week 36