Image-Guided Biopsies in Identifying Mechanisms of Resistance in Participants With Metastatic Castration Resistant Prostate Cancer Undergoing Radioligand Therapy

PRIMARY OBJECTIVES:

I. Proportion of metastatic castration resistant prostate cancer (mCRPC) patients with
altered signaling pathways after radioligand therapy assessed by phospho-proteomics of biopsy
samples.

SECONDARY OBJECTIVES:

I. Generation of patient derived xenograft (PDX) models to determine if tumor levels of
activity for individual adaptive pathways are related to the best prostate specific antigen
(PSA) response.

II. Sequencing to identify frequently mutated genes such as TP53 and ATM.

OUTLINE:

Participants undergo image-guided biopsy over 45 minutes prior to first RLT course and 1-2
days after the third RLT course.

Inclusion Criteria:

- Volunteer patient

- Histologically confirmed prostate cancer

- Enrolled in Lu-PSMA-617 treatment trial (Institutional Review Board [IRB]# 17-000330)

- Based on positron emission tomography (PET)/computed tomography (CT) images: evidence
of lymph node or soft tissue metastatic disease amenable to image-guided biopsy

- Platelets > 75,000/ul within 14 days prior to biopsy

- Prothrombin time (PT) or international normalized ratio (INR) and a partial
thromboplastin time (PTT) < 1.5 times the institutional upper limit of normal (ULN)
within 14 days prior to biopsy

- Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are
deemed able to tolerate discontinuation of anti-coagulation for one week prior to the
biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per
local standard operating procedures, provided there is agreement regarding the
procedure between the treating physician, the interventional radiologist and the
principal investigator (PI)

Exclusion Criteria:

- Patients with significant congenital or acquired bleeding disorders (e.g. von
Wildebrand's disease, acquired bleeding factor inhibitors) are not eligible