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
Vadim S Koshkin
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.
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 O…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Participants must have histologically or cytologically confirmed prostate cancer. Either fresh biopsy or archival tissue can be used for confirmation. 2. Age \>= 18 years. 3. Patients must have metastatic castration resistant prostate cancer (mCRPC) with progression based on Prostate Cancer Working Group 3 (PCWG3) criteria. 4. Patients must have adenocarcinoma histology. 5. Prior treatment with at least one novel hormonal agents (NHA) such as abiraterone acetate, enzalutamide, apalutamide, darolutamide etc. 6. Patients must have prior orchiectomy and/or ongoing androgen…
Interventions
- DrugAbemaciclib
Given Orally
- DrugLutetium Lu 177-PSMA-617
Given IV
Location
- University of California, San FranciscoSan Francisco, California