Study of Pembrolizumab and Radiotherapy in Liver Cancer

NCT03316872 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PEMRAD
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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).

  3 years

Secondary Outcomes (2)

• Progression-free Survival

  3 years

• Overall Survival Rate

  3 years

Study Arms (1)

Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)

EXPERIMENTAL

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.

Drug: Pembrolizumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

Pembrolizumab DRUG

Pembrolizumab is a humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Also known as: KEYTRUDA

Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)

Stereotactic Body Radiotherapy (SBRT) RADIATION

SBRT involves delivery of high doses of radiation therapy in smaller fractions

Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Smaller satellites of HCC or non-definite HCC need not be encompassed within SBRT volumes if needed to respect normal tissue limits.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have demonstrated disease progression, after previous treatment with sorafenib for advanced or metastatic disease, lasting a minimum of 8 week period, allowing for appropriate interruptions and dose reductions.
• Have recovered (to ≤ grade 1) from prior toxicities related to previous treatments at the time of study enrollment, with the exception of alopecia or skin depigmentation.

You may not qualify if:

• 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).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known history of prior invasive malignancy except if the subject has undergone curative-intent therapy with no evidence of disease recurrence for 2 years prior to study entry. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, low-risk prostate cancer or in situ cervical cancer.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Jennifer J Knox
• Organization: Princess Margaret Cancer Centre

jennifer.knox@uhn.ca

+1-416-946-2399

Study Officials

• Jennifer J. Knox, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: October 20, 2017
• Study Start: February 15, 2018
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: July 25, 2025
• Results First Posted: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)