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Advanced Adult Hepatocellular CarcinomaNCT02072486

Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

A study testing Laboratory Biomarker Analysis and Sorafenib Tosylate in people with Advanced Adult Hepatocellular Carcinoma and Localized Non-Resectable Adult Hepatocellular Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Laboratory Biomarker Analysis and Sorafenib Tosylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
18 Nov 2013to 19 Jul 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Granzyme B Production as a Biomarker for the Immunomodulatory Activity of Sorafenib in HCC

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether the proportion of cytotoxic T lymphocytes that are producing granzyme B (denoted pGrzB) as measured ~28-35 days after initiation of sorafenib (sorafenib tosylate) therapy correlates with overall survival, defined as the number of months between the start of sorafenib treatment and death from any cause.

SECONDARY OBJECTIVES:

  1. To determine whether higher pGrzB levels will correlate with better sorafenib tolerance, manifested by fewer dose reductions, dose interruptions and adverse events.

II. To determine whether improved immune function may also result in greater recognition of hepatitis viral antigens.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up for 30 days or after the 6 month time point if continuing sorafenib tosylate and then periodically thereafter.

Being tested
Laboratory Biomarker Analysis, Sorafenib Tosylate
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

    Given PO

Study groups in NCT02072486
Study groupRoleWhat they receive
Treatment (sorafenib tosylate)ExperimentalPatients receive sorafenib tosylate PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Sorafenib Tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 35 days

  2. 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.

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

Secondary outcomes (1)

  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

    These differences will be assessed using permutation independent sample t-tests. For an AE observed in 15 (50%) of the patients and two-sided statistical significance threshold = 0.05, this test has 80% power to detect a 1.0 standard difference in mean pGrzB. 95% confidence limits for the difference in mean pGrzB will also be provided. Descriptive statistics include the pGrzB mean, standard deviations and ranges within AE or patient characteristics.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2014 (estimated)
  2. Study start18 Nov 2013
  3. Primary completion19 Jul 2019
  4. Study completion19 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02072486
Sponsor's protocol ID
I 238913
Other IDs
NCI-2014-00180, I 238913
Status last verified
Jul 2022
First submitted
24 Feb 2014
Last updated
25 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 31391334

Questions about this trial

What is this clinical trial studying?

A study testing Laboratory Biomarker Analysis and Sorafenib Tosylate in people with Advanced Adult Hepatocellular Carcinoma and Localized Non-Resectable Adult Hepatocellular Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Granzyme B levels (time frame: Up to 35 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02072486, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2022.

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