A Radioactive Drug (177Lu–PSMA-617) for the Treatment of PSMA Positive Metastatic and/or Unresectable Liver Cancer
This phase I trial studies the feasibility, safety, and side effects of a radioactive drug called 177Lu–PSMA-617, and evaluates its effect in treating patients with prostate-specific membrane antigen (PSMA) positive hepatocellular carcinoma (liver cancer) that has spread from where it first started to other places in the body (metastatic) and/or that cannot be removed by surgery (unresectable). 177Lu–PSMA-617 binds to the PSMA protein, which is found on liver tumor cells. 177Lu–PSMA-617 builds up in these cells and gives off radiation that may kill them.
Inclusion Criteria
- Subjects must have histologically, cytologically or radiographically confirmed hepatocellular carcinoma by Liver Imaging Reporting and Data System (LI-RADS) with metastatic and/or unresectable disease
- Subjects must have received one prior line of systemic therapy for the treatment of metastatic and/or unresectable HCC including anti-PD-L1 therapy. Subjects will be enrolled at the time of progression on first-line therapy for metastatic and/or unresectable disease
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of 177Lu–PSMA-617 (Lu-177 vipivotide tetraxetan) in subjects < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 75,000/mcL
- Serum creatinine ≤ 1.5 x institutional upper limit of normal or creatinine clearance (CrCl) ≥ 60 mL/min using the Cockroft-Gault formula for subjects with creatinine levels > 1.5 upper limit of normal (ULN)
- Child-Pugh class A or B7
- At least one target lesion measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- PSMA-PET demonstrating PSMA PET positive lesion (higher uptake in the tumor compared with background liver uptake)
- Subjects must have the ability to understand and the willingness to sign a written informed consent document
- Subjects of childbearing age are using an appropriate method of contraception
Exclusion Criteria
- Subjects receiving any other investigational agents
- Subject has received investigational therapy within 4 weeks or within 5 half-lives of the therapeutic agent (whichever is shorter)
- Ongoing grade 3 or higher toxicity from prior anticancer systemic therapy
- Prior treatment with yttrium Y90 (Y90) radioembolization for hepatocellular carcinoma
- Subjects who have undergone major surgery within 3 months of screening and have not adequately recovered
- Known additional malignancy that currently requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Subjects with untreated brain metastases and/or carcinomatous meningitis will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Subjects with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases and are not using steroids for at least 7 days prior to trial treatment
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Subjects with known psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the treating investigator
- Subject is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months for females and 14 weeks for males after the last dose of trial treatment. Pregnant or breastfeeding women are excluded from this study because 177Lu–PSMA-617 has not been previously studied in this population and the potential for teratogenic or abortifacient effects are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to the treatment of the mother with 177Lu–PSMA-617, breastfeeding should be discontinued if the mother is treated with 177Lu–PSMA-617. These potential risks may also apply to 68Ga-PSMA-11 used in this study
- Subject has received live vaccine within 30 days prior to the first dose of trial treatment
- Subject with recent variceal bleeding, gastrointestinal bleeding or high risk of bleeding
Additional locations may be listed on ClinicalTrials.gov for NCT06852820.
Locations matching your search criteria
United States
Ohio
Cleveland
PRIMARY OBJECTIVES:
I. To determine feasibility of PSMA-positron emission tomography (PET) in patients with metastatic and/or unresectable hepatocellular carcinoma (HCC).
II. To determine safety and tolerability of lutetium Lu 177 vipivotide tetraxetan (177Lu–PSMA-617) monotherapy in patients with PSMA PET-positive HCC as measured by the frequency and grade of adverse events.
SECONDARY OBJECTIVES:
I. To determine the 12-week progression free survival (PFS) and median PFS with 177Lu–PSMA-617 in patients with PSMA PET-positive HCC.
II. To determine the objective response rate (ORR) with 177Lu–PSMA-617 in patients with PSMA PET-positive HCC.
III. To assess overall survival (OS).
IV. To assess clinical benefit rate.
EXPLORATORY OBJECTIVES:
I. To demonstrate the dosimetry and biodistribution of 177Lu–PSMA-617 in HCC using quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT).
II. To assess the association of PSMA expression by PSMA-PET and tumor radiation dose measured by SPECT/CT with clinical response.
CORRELATIVE OBJECTIVES:
I. To correlate the clinical outcomes with PSMA expression by immunohistochemistry (IHC).
II. To determine if changes in the fraction and mutational profile of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and quantity of PSMA-positive circulating tumor cells (CTCs) before, during and after treatment and correlate with response.
III. To define changes in fecal and oral microbial profile by 16S ribosomal ribonucleic acid (rRNA) sequencing following treatment with 177Lu–PSMA-617.
IV. To correlate alpha-fetoprotein (AFP) with response.
OUTLINE:
Patients receive 177Lu–PSMA-617 intravenously (IV) on day 1 of each cycle. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gallium Ga 68 gozetotide IV and undergo PET (68Ga-PSMA-11 PET) scans, CT or CT/magnetic resonance imaging (MRI) scans, and SPECT/CT scans throughout the study. In addition, patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days, then every 3 months in year 1, every 4-6 months in year 2, and then every 6 months in years 3, 4, and 5.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorMelissa Amy Lumish
- Primary IDCASE7224
- Secondary IDsNCI-2025-06673
- ClinicalTrials.gov IDNCT06852820