NCT02072486

Brief Summary

This clinical trial studies sorafenib tosylate in treating patients with liver cancer that cannot be removed by surgery. Sorafenib tosylate may block some of the enzymes needed for tumor cell growth. Blocking these enzymes may also help the immune system work better. Granzyme B is a biomarker that can be used to measure how well the immune system is working. A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. Studying granzyme B levels in patients receiving sorafenib tosylate may help doctors learn more about the effects of sorafenib tosylate on the immune system and may help to predict how well sorafenib tosylate will work in treating patients with liver cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2013

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 18, 2013

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

February 24, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 26, 2014

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 19, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

July 19, 2020

Completed
Last Updated

July 25, 2022

Status Verified

July 1, 2022

Enrollment Period

5.7 years

First QC Date

February 24, 2014

Last Update Submit

July 20, 2022

Conditions

Advanced Adult Hepatocellular CarcinomaLocalized Non-Resectable Adult Hepatocellular CarcinomaStage III Childhood Hepatocellular CarcinomaStage IIIA Hepatocellular CarcinomaStage IIIB Hepatocellular CarcinomaStage IIIC Hepatocellular CarcinomaStage IV Childhood Hepatocellular CarcinomaStage IVA Hepatocellular CarcinomaStage IVB Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

  • Granzyme B levels

    The pGrzB hazard ratio (per 10 percentage point increase) and the associated 95% confidence interval will be estimated using a Cox PH model. Whether pGrzB measurements vary by presence of grade 3+ adverse events (AEs) will be assessed using permutation independent sample t-tests. Descriptive statistics include the pGrzB mean, standard deviations and ranges within AE or patient characteristics.

    Up to 35 days

  • Overall survival (OS)

    The hazard ratio and 95% confidence interval for the effect of day \~28-35 pGrzB (in 10 percentage point increments) on OS will be estimated using proportional hazards (PH) models. The pGrzB functional form will be assessed using generalized additive models. Possible confounding from sorafenib dose differences and baseline characteristics will be assessed by including other covariates (or perhaps frailty terms) in the model.

    Time between start of first treatment and death, assessed up to 6 months

Secondary Outcomes (1)

  • Granzyme B level variations by presence of grade 3 or higher AE, characterized using National Cancer Institute Common Terminology Criteria for Adverse Events severity grade

    Up to 30 days

Other Outcomes (2)

  • Change in granzyme B levels after sorafenib tosylate treatment

    Baseline to up to 35 days

  • Proportion of cluster of differentiation (CD)8+ T cells expressing granzyme B

    Up to 24 weeks

Study Arms (1)

Treatment (sorafenib tosylate)

EXPERIMENTAL

Patients receive sorafenib tosylate PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker AnalysisDrug: Sorafenib Tosylate

Interventions

Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (sorafenib tosylate)
Sorafenib TosylateDRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Treatment (sorafenib tosylate)

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Subject or legal representative 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
  • Outpatients with histologically/cytologically documented or radiographically diagnosed unresectable hepatocellular carcinoma (HCC) who are candidates for systemic therapy and for whom a decision to treat with sorafenib has been made; radiographic diagnosis needs typical findings of HCC by a radiographic method, i.e. on multi-dimensional dynamic computed tomography (CT), CT hepatic arteriography (CTHA)/CT arterial portography (CTAP) or magnetic resonance imaging (MRI)
  • Patients must have a life expectancy of at least 8 weeks
  • Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding

You may not qualify if:

  • 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
  • Pregnant or nursing female subjects
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
  • Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib; prior treatment with liver directed, ablative or surgical therapies will be permitted as long as there is documented progression justifying the need for starting sorafenib therapy
  • No known contraindications to anti-angiogenics such as severe coronary artery disease, recent myocardial infarction or stroke within 6 months, bleeding peptic ulcer or varices within last 3 months, and any other major illness that may jeopardize study treatment or follow up

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Related Publications (1)

  • Kalathil SG, Hutson A, Barbi J, Iyer R, Thanavala Y. Augmentation of IFN-gamma+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy. JCI Insight. 2019 Aug 8;4(15):e130116. doi: 10.1172/jci.insight.130116. eCollection 2019 Aug 8.

    PMID: 31391334DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Renuka Iyer

    Roswell Park Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 24, 2014

First Posted

February 26, 2014

Study Start

November 18, 2013

Primary Completion

July 19, 2019

Study Completion

July 19, 2020

Last Updated

July 25, 2022

Record last verified: 2022-07

Locations

US(1)