Clinical Trial · NCT05570994

177Lu-HTK03170 in mCRPC With PSMA Positive Disease

Overview

This study will determine the safe initial injected activity of the radioligand therapy 177Lu-HTK03170 for the measurement of dosimetry and initiation of treatment in subjects with PSMA-positive, metastatic castrate resistant prostate cancer, (mCRPC). Subjects will receive treatment which will be escalated between cycles and personalized based on dosimetry calculations and imaging. In addition, antitumour activity will be measured by radiographic response, and further assessments of the treatment will be measured by CT imaging, ctDNA/ctRNA, PSA, PSMA PET/CT, and quality of life questionnaires. Subjects will be followed for 2 years or until they have progression and are switched to another systemic treatment.

Sponsor

British Columbia Cancer Agency

Phase

Phase 1/2

ClinicalTrials.gov

NCT05570994

Eligibility

Inclusion

Willing and able to provide consent
Progression on treatment with abiraterone and/or enzalutamide, or similar next generation ARAT therapy, as determined by the investigator. Subjects who have received docetaxel in the castration-resistant setting are also eligible to participate. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor is permitted.
Must be surgically sterile or use adequate contraception for the duration of the therapy and 6 months after the end of therapy
Soft tissue disease progression on chest, abdomen, pelvis CT or magnetic resonance imaging (MRI; RECIST v1.1)
Recovery from all previous cancer treatment toxicities to grade ≤ 2 (as per CTCAE 4.03)
Pathologically confirmed prostate adenocarcinoma
Eastern Cooperative Oncology Group (ECOG) performance score ≤2
Prior orchiectomy, or if on luteinizing hormone releasing hormone (LHRH) agonist/antagonist, then testosterone \< 1.7 nmol/L or \< 50 ng/dL
Each subject must meet all of the following inclusion criteria to be enrolled in the study:
Prostate-specific antigen progression: two consecutive rising PSA values from a baseline measurement with an interval of ≥ 1 week between measurements. Minimum PSA at screening visit is ≥ 2.0 µg/L.
Able to comply with scheduled visits, treatment plans, laboratory tests, imaging tests, and other procedures required and detailed in the protocol.
Life expectancy of \> 6 months
Bone progression: ≥ 2 new lesions on bone scan
Subjects must have evidence of biochemical or imaging progression. Progression is defined as any one of the following:

Exclusion

Prior treatment with 225Ac-PSMA-617, 177Lu-PSMA, other radiolabeled therapeutic PSMA-ligands, or radio-immunotherapy
Active epidural disease (treated epidural disease is permitted)
Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or targeted therapy) within 28 days prior to day of enrollment
Clinically significant cardiac disease including:
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
History of risk factors for xerostomia (ie, head and neck radiation, Sjögren's disease) or pre-existing xerostomia Grade ≥1
Major surgery within 4 weeks of starting study treatment.
Known parenchymal brain metastases
History of unstable angina pectoris, symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry.
Radiotherapy to target lesions (measurable disease) ≤ 4 weeks prior to enrolment
History of documented congestive heart failure (New York Heart Association \[NYHA\] functional classification III-IV) or cardiomyopathy.
Unmanageable urinary tract obstruction or hydronephrosis