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Clinical Trial 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.


Clinical Trial 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 (PROMOTE). II. To assess changes in PSMA expression in biopsies at the time of progression relative to pre-treatment biopsies using immunohistochemistry (IHC). III. To describe PSMA upregulation on imaging following 7 days of treatment with abemaciclib, and in particular compare to PSMA upregulation on imaging seen following 14 days of abemaciclib treatment. IV. To describe PSMA expression and upregulation on imaging following combined treatment with abemaciclib and 177Lu-PSMA-617 at the time of subsequent therapy cycles (pre and post abemaciclib treatment with cycle 3) in some patients treated with RP2D in Part B (expansion cohort). V. To describe patterns of progression following completion of treatment, including in patients with available 68Ga-PSMA-11 PET scans. VI. To compare response to treatment and clinical outcomes with different dose levels of abemaciclib used in this study. OUTLINE: This is a dose-escalation study of abemaciclib. Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 and lutetium Lu 177 vipivotide tetraxetan intravenously (IV) over 30 minutes on day 15. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study intervention, patients are followed up at 30 days, and then every 3 months for up to 2 years. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05113537
Study type Interventional
Source University of California, San Francisco
Contact Audrey Phone
Phone (415) 476-7544
Email [email protected]
Status Not yet recruiting
Phase Phase 1/Phase 2
Start date December 31, 2021
Completion date December 31, 2026

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