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

TheraPb-ADVC001

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).

2023-03-15

2024-06-01

2024-06-01

Recruiting

Early phase I

18

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This is a single arm, non-randomized study based on a 3 + 3 design modified to incorporate measures of both toxicity and tumour response.\n\nA minimum of 3 participants will be treated at each dose level and evaluated for dose limiting toxicity for 6 weeks before consideration is made to enroll the next cohort of participants and dose escalate. Four dose levels will be considered, namely 60 MBq, 90 MBq, 120 MBq and 150 MBq of \\[212Pb\\]Pb-ADVC001.\n\nUp to 4 cycles of \\[212Pb\\]Pb-ADVC001 will be administered at 6 weekly intervals. Dose levels can be de-escalated across subsequent cycles to manage any toxicity if participants show tumour response.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 18, 'type': 'ESTIMATED'}}

2023-11-03