Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer
brief summary
This phase I/II trial tests the safety, side effects, and best dose of abemaciclib and whether it works before 177Lu-PSMA-617 in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abemaciclib is in a class of medications called kinase inhibitors. It is highly selective inhibitors of cyclin-dependent kinase 4 and 6, which are proteins involved in cell differentiation and growth. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. Radioligand therapy uses a small molecule (in this case 177Lu-PSMA-617), which carries a radioactive component to destroys tumor cells. When 177Lu-PSMA-617 is injected into the body, it attaches to the prostate-specific membrane antigen (PSMA) receptor found on tumor cells. After 177Lu-PSMA-617 attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving abemaciclib before 177Lu-PSMA-617 may help 177Lu-PSMA-617 kill more tumor cells.
detailed description
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for abemaciclib given as lead-in treatment prior to lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) for each treatment cycle, as well as dose limiting toxicities (DLTs) of this combination regimen. (Part A)
II. To determine the change in prostate-specific membrane antigen (PSMA) uptake on gallium Ga 68 gozetotide (68Ga-PSMA-11) positron emission tomography (PET) scan following fourteen days of priming with abemaciclib treatment, relative to the pre-treatment baseline scan. (Part B (Expanded Cohort)).
SECONDARY OBJECTIVES:
I. To determine the (proportion of patients who experience \>= 50% decline from baseline in serum prostate specific antigen (PSA) (PSA50) response of this combination treatment. (Part B \[Expanded Cohort\]) II. To describe the safety of this combination treatment regimen using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0. (Part B \[Expanded Cohort\]) III. To determine the radiographic progression free survival (rPFS) according to Prostate Cancer Working Group 3 (PCWG3) guidelines among patients treated with this combination regimen. (Part B \[Expanded Cohort\]) IV. To determine the objective response rate (ORR) (complete response \[CR\] + partial response \[PR\]) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response in soft tissue, lymph node and visceral lesions. (Part B \[Expanded Cohort\]) V. To determine the disease control rate (DCR) (CR + PR + stable disease (SD)) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. (Part B \[Expanded Cohort\]) VI. To determine the overall survival (OS) of patients treated with this combination regimen. (Part B \[Expanded Cohort\]) VII. To determine the median duration of response (DOR) in patients treated with this combination regimen who achieve CR or PR as measured by RECIST v1.1. (Part B \[Expanded Cohort\])
EXPLORATORY OBJECTIVES:
I. To assess changes in tumor microenvironment using ribonucleic acid (RNA) and whole exome sequencing by comparing biopsies obtained pre and post-combination treatment using the established institutional biopsy protocol (PSMA biopsy study).
II. To assess changes in PSMA expression in biopsies at the time of progression relative to pre-treatment biopsies using immunohistochemistry (IHC).
official title
Phase I/II Study of CDK4/6 Inhibition With Abemaciclib to Upregulate PSMA Expression Prior to 177Lu-PSMA-617 Treatment in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Previously Treated With Novel Hormonal Agents and Chemotherapy