Actively Recruiting
Phase I/II Study of CDK4/6 Inhibition With Abemaciclib to Increase PSMA Expression Before 177Lu-PSMA-617 Treatment in Metastatic Castrate Resistant Prostate Cancer Previously Treated With Hormonal Agents and Chemotherapy
Led by Vadim S Koshkin · Updated on 2026-04-13
30
Participants Needed
1
Research Sites
82 weeks
Total Duration
On this page
Sponsors
V
Vadim S Koshkin
Lead Sponsor
P
Prostate Cancer Foundation
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying metastatic castration-resistant prostate cancer (mCRPC) that has spread to other parts of the body. The trial evaluates the safety, side effects, best dose, and potential effects of giving abemaciclib before the radioligand therapy 177Lu-PSMA-617. Abemaciclib blocks proteins that help cancer cells grow, while 177Lu-PSMA-617 targets and destroys tumor cells by attaching to a prostate tumor marker called PSMA. The study explores whether abemaciclib can help 177Lu-PSMA-617 kill more tumor cells. The trial has two parts. In Part A, patients receive escalating doses of abemaciclib orally twice daily for 14 days, followed by an intravenous infusion of 177Lu-PSMA-617 on day 15. This treatment cycle repeats every 6 weeks for up to 4 cycles if the cancer does not progress or side effects are acceptable. In Part B, patients receive the recommended phase 2 dose of abemaciclib with the same schedule. The study also uses PET scans to measure changes in PSMA expression before and after abemaciclib treatment. Participants will have regular imaging scans, blood tests including prostate-specific antigen (PSA), and monitoring for side effects using standard criteria. Researchers will assess tumor responses, progression-free survival, overall survival, and changes in tumor biology through biopsies and sequencing. After treatment, patients are followed up at 30 days and then contacted every 3 months for long-term survival tracking until the study ends or consent is withdrawn.
CONDITIONS
Brief Title
Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must have confirmed prostate cancer by biopsy or cytology
- Age 18 years or older
- Have metastatic castration resistant prostate cancer with progression as per PCWG3 criteria
- Have adenocarcinoma histology
- Prior treatment with at least one novel hormonal agent such as abiraterone acetate, enzalutamide, apalutamide, or darolutamide
- Prior orchiectomy or ongoing androgen-deprivation therapy with castrate serum testosterone levels (< 50 ng/dL or < 1.7 nmol/L)
- 68Ga-PSMA-11 PET scan showing at least one PSMA-positive lesion with SUVmax greater than liver
- Eastern Cooperative Oncology Group performance status 0 to 2
- Life expectancy greater than 6 months
- Adequate organ and bone marrow function as specified including WBC > 2.5, ANC > 1.5, hemoglobin >= 8.0, platelets >= 100, total bilirubin <= 1.5x ULN (or <= 2x ULN for Gilbert's Syndrome), AST and ALT <= 3x ULN (or <= 5x ULN if liver metastases), creatinine <= 1.5x ULN or GFR >= 30 mL/min/1.73 m2
- Ability to swallow oral medications
- Ability to understand and sign informed consent
- HIV-positive patients on effective therapy with undetectable viral load within 6 months are eligible
- Patients with controlled hepatitis B or cured hepatitis C infection
- Patients with other prior or current malignancies not interfering with study
- Agreement to use effective contraception during and for 2 months after treatment
You will not qualify if you...
- Small cell or neuroendocrine carcinoma histology
- Super scan on baseline bone scan (diffuse skeletal uptake)
- Prior treatment with CDK4/6 inhibitors
- Prior treatment with PSMA-targeted radioligand therapy (except CAR-T or BiTEs)
- Radium-223 treatment within 6 weeks before study entry
- Systemic anti-cancer therapy within 3 weeks before study entry
- Significant or unresolved radiation-related adverse events (grade 3 or higher)
- History of central nervous system metastases unless treated and asymptomatic without steroids
- Symptoms or risk of spinal cord compression
- Serious concurrent medical conditions as judged by investigator
- Other malignancies expected to affect life expectancy or assessment
- Not recovered from adverse events of prior therapy to grade 1 or baseline except alopecia or neuropathy
- Serious uncontrolled medical conditions like interstitial lung disease, severe dyspnea, major stomach or bowel surgery, Crohn's disease, ulcerative colitis, or ongoing severe diarrhea
- Active systemic bacterial, fungal, or viral infections
- Personal history of cardiovascular syncope, ventricular arrhythmia, or sudden cardiac arrest
- Currently receiving other investigational treatments
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 14 days per cycle
Participants take abemaciclib orally twice daily for 14 days to prime PSMA expression before receiving the radioligand treatment.
Up to 4 cycles every 6 weeks with 14 days of oral medication per cycle
Duration - Up to 4 cycles, each 6 weeks long
Participants receive lutetium Lu 177-PSMA-617 intravenously on day 15 of each 6-week cycle following abemaciclib priming, repeated for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Up to 4 intravenous infusions every 6 weeks
Duration - Up to 2 years or longer until study ends or withdrawal
Participants are followed for safety and overall survival with visits at 30 days post-treatment and then approximately every 3 months until study conclusion or withdrawal.
1 visit 30 days after last treatment and then visits approximately every 3 months
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
Research Team
U
UCSF Genitourinary Medical Oncology Recruitment
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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