Pembrolizumab and Stereotactic Radiotherapy Combined in Subjects With Advanced Hepatocellular Carcinoma - A Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- University Health Network, Toronto
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Overall Response Rate
- Status
- Terminated
- Last Updated
- 9 months ago
Overview
Brief Summary
This is a phase 2 study whose purpose is to assess the efficacy of the combination of pembrolizumab and stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after treatment with sorafenib.
Detailed Description
Pembrolizumab will be administered intravenously as a 30-minute infusion at a dose of 200 mg every 21 days, until disease progression or intolerable toxicity. Stereotactic radiotherapy will commence on day 2 of the first cycle of pembrolizumab, and will be delivered in 5 fractions over 8-15 days in accordance with institutional protocol. Subjects will be re-evaluated for response every 12 weeks. In addition to a baseline scan, confirmatory scans should also be obtained 4-8 weeks following initial documentation of objective response. Response and progression will be evaluated in this study using both RECIST 1.1and (iRECIST) guideline (Seymor 2017).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent/assent for the trial
- •Be ≥18 years of age on day of signing informed consent.
- •Have a histologically- or cytologically-confirmed diagnosis of hepatocellular carcinoma (HCC), and at least one measurable lesion.
- •Have current liver function meeting Child Pugh Class A (5-6 points), with no encephalopathy or ascites.
- •Have intrahepatic HCC amenable to stereotactic body radiotherapy (SBRT):
- •maximum 10 lesions to be treated, and
- •total tumor diameter to be treated \<20 cm
- •No single liver tumor \>15 cm in diameter
- •No evidence of common or main branch bile duct invasion
- •No evidence of direct tumor extension into stomach, duodenum, small bowel, large bowel or diaphragm
Exclusion Criteria
- •Has received any second-line systemic therapy for advanced HCC after disease progression following sorafenib therapy, or has had prior radiotherapy to the proposed treatment field.
- •Is currently participating and receiving experimental treatment as part of a clinical trial, or has participated in a study of an immune checkpoint inhibitor and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment.
- •Has had a previous solid organ transplant, a diagnosis of immunodeficiency, or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has liver tumor not amenable to SBRT, or has had prior upper abdominal radiation therapy within planned volumes (exceeding standard tolerances).
- •Has a histological or cytological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC.
- •Has had prior radioembolization or other selective internal radiotherapy treatment to the liver.
- •Has dual active HBV infection (HBsAg (+) and/or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry.
- •Has had esophageal or gastric variceal bleeding within 3 months prior to study enrollment.
- •Has had encephalopathy in the past 6 months, or has clinically apparent ascites at the time of study enrollment.
- •Has a known history of active TB (Bacillus Tuberculosis).
Arms & Interventions
Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)
Pembrolizumab, intravenously, at a dose of 200 mg, once every 3 weeks SBRT starting Day 2 of Cycle 1 of pembrolizumab treatment, given in 5 fractions over 10-15 days.
Intervention: Pembrolizumab
Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)
Pembrolizumab, intravenously, at a dose of 200 mg, once every 3 weeks SBRT starting Day 2 of Cycle 1 of pembrolizumab treatment, given in 5 fractions over 10-15 days.
Intervention: Stereotactic Body Radiotherapy (SBRT)
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: 3 years
To assess the systemic efficacy of combined SBRT and pembrolizumab in subjects with advanced HCC who have experienced disease progression after previous therapy, as measured by overall response rate (ORR).
Secondary Outcomes
- Progression-free Survival(3 years)
- Overall Survival Rate(3 years)