Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

NCT03211416 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: I 35316NCI-2017-01114
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This phase Ib/II trial studies how well sorafenib tosylate and pembrolizumab work in treating patients with liver cancer that has spread to other parts of the body. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving sorafenib tosylate and pembrolizumab may work better in treating patients with liver cancer.

Conditions

Advanced Adult Hepatocellular Carcinoma; Child-Pugh Class A; Stage III Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate Defined as Partial or Complete Response Per Immune-related Response Evaluation Criteria in Solid Tumors

  The response rate will be estimated as the binomial proportion of responders among evaluable patients, and supported by Jeffreys? 95% confidence interval.

  Up to 6 months

Secondary Outcomes (2)

• Overall Survival

  From the date of study enrollment to the time of death from any cause, assessed up to 3 year

• Time to Tumor Progression

  From the date of study enrollment to the first observation of progressive disease, assessed up to 3 years

Other Outcomes (2)

• Change in Functional Activity of Effector T Cells

  Up to 3 years

• Change in Levels of Immunosuppressive Cells

  Up to 3 years

Study Arms (1)

Treatment (sorafenib tosylate, pembrolizumab)

EXPERIMENTAL

Patients receive sorafenib tosylate PO BID on days -28 to -1 and 1-21. Patients also receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Sorafenib Tosylate

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (sorafenib tosylate, pembrolizumab)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (sorafenib tosylate, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sorafenib tosylate, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Participant must have histologically or radiographically confirmed hepatocellular cancer (HCC) that is advanced or metastatic and if archival tissue is available, have archival tissue submitted for PD-L1, PD-L2 testing
• Participants with measurable disease that has progressed are eligible if prior surgery or locoregional therapy occurred \> 28 days prior to enrollment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky \>= 60%)
• Child-Pugh class-A liver function
• Absolute neutrophil count (ANC) \>= 1,500/ mcL
• Hemoglobin \>= 8.5 g/dL
• Platelets \>= 75,000/ mcL
• Total bilirubin =\< 2.0 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 X ULN
• Serum Creatinine \<= 1.5 upper limit of normal (ULN)or Creatinine clearance \> 50 mL/minute if serum creatinine is elevated above 1.5 X ULN
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Ability to swallow and retain oral medication
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• Participants with past or ongoing hepatitis C virus (HCV) infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention.

You may not qualify if:

• One prior line of therapy that may include a PDL1 blocker allowed, no prior sorafenib or PD1 blocker allowed.
• Participants who have had radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Any evidence of bleeding diathesis (patients on therapeutic warfarin or heparin will be excluded)
• Participants with a history of variceal bleed within 6 months prior to enrollment
• Known human immunodeficiency virus (HIV)-positive participants (even if on combination retrovirals, participant will be excluded
• Participants with chronic autoimmune disease
• Participants with known brain metastases should be excluded from this clinical trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
• Received a live vaccine within 30 days prior to start of study treatment

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab; Sorafenib

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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Kris Attwood
• Organization: Roswell Park Comprehensive Cancer Center

Kris.Attwood@roswellpark.org

8772757724

Study Officials

• Kannan Thanikachalam, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 7, 2017
• Study Start: December 7, 2017
• Primary Completion: March 7, 2023
• Study Completion: August 15, 2025
• Last Updated: February 5, 2026
• Results First Posted: May 29, 2024

Record last verified: 2026-02

Locations

US (2)