68Ga PSMA PET Imaging for the Treatment of Advanced Liver Cancer

Study Overview
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Brief Summary
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This phase II trial tests whether 68-Gallium prostate specific membrane antigen (68Ga-PSMA) positron emission tomography (PET) imaging can improve the diagnosis and management of liver cancer that has spread to other parts of the body (advanced). PSMA is a protein that appears in large amounts on the surface of liver cancer cells. The radioactive chemical compound (68Ga-PSMA) has been designed to circulate through the body and attach itself to the PSMA protein on liver cancer cells. A PET scan is then used to detect the location of the tumor cells. 68Ga-PSMA PET may improve upon the diagnosis and management of liver cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To test the performance of novel biomarkers derived from PSMA PET/computed tomography (CT) to measure response compared to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in advanced hepatocellular carcinoma (HCC) patients treated with immunotherapy. II. To identify precision imaging biomarkers that can predict response of HCC to novel immunotherapy. OUTLINE: Patients undergo 68GA PSMA PET/CT scans at baseline, and after 3, 6, 9, and 12 cycles of standard of care immunotherapy in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed-up every 6 months for 3 years.

Official Title
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Optimizing Outcomes of Patients With Advanced HCC Undergoing Immunotherapy Through Novel 68Ga PSMA PET Imaging

Conditions
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Advanced Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8, Stage IVB Hepatocellular Carcinoma AJCC v8, Unresectable Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: Computed Tomography
* Drug: Gallium Ga 68 Gozetotide
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with pathologically confirmed HCC not amenable to curative resection, transplantation or ablative therapies Have radiographically measurable disease by RECIST Eligible for atezolizumab/bevacizumab front line therapy Male or female with age greater than 18 years, with the capacity and willingness to provide written informed consent Exclusion Criteria: Pregnant and/or breast-feeding patients. A negative pregnancy test within 48 hours of the PET scan Patients with higher than the weight/size limitations of PET/CT scanner

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (68GA PSMA PET/CT)<br>Patients undergo 68GA PSMA PET/CT scans at baseline, and after 3, 6, 9, and 12 cycles of standard of care immunotherapy in the absence of disease progression or unacceptable toxicity. | Procedure: Computed Tomography<br>* Undergo 68Ga PSMA PET/CT<br>* Other names: tomography;Drug: Gallium Ga 68 Gozetotide<br>* Undergo 68Ga PSMA PET/CT<br>* Other names: PSMA-HBED-CC GA-68;Procedure: Positron Emission Tomography<br>* Undergo 68Ga PSMA PET/CT<br>* Other names: PT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment response | Time to response, per RECIST 1.1 and per PSMA PET/CT, will be correlated to each other using Cox proportional hazard model with response per RECIST 1.1 as the dependent variable and the time to response per PSMA PET/CT will be included in the model as a time-varying covariate. | Time from study registration to complete response/partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and per PSMA positron emission tomography (PET)/computed tomography (CT), assessed up to 12 cycles of treatment or 36 weeks | 
| Progression free survival (PFS) | Will be calculated among PSMA PET/CT positive patients using Kaplan-Meier method with corresponding confidence interval calculated using Greenwood's formula. In PSMA negative patients, will explore the potential prognostic effect of PSMA status on PFS using Cox proportional hazard model with PSMA PET/CT status (positive versus negative) as the main variable of interest while adjusting for other potential confounders. | At 6 months | 
| Time to progression | RECIST 1.1 and PSMA PET/CT will be correlated to each other using Cox proportional hazard model with response per RECIST 1.1 as the dependent varible and the time to response per PSMA PET/CT will be included in the model as a time-vaying covariate. | Time from study registration to disease progression per RECIST 1.1 and per PSMA PET/CT, assessed up to 3 years |