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.
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
- Conditions the study is for
- Advanced Adult Hepatocellular Carcinoma, Localized Non-Resectable Adult Hepatocellular Carcinoma, Stage III Childhood Hepatocellular Carcinoma
- 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
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
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:
- 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:
- 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.
- Conditions
- Advanced Adult Hepatocellular Carcinoma, Localized Non-Resectable Adult Hepatocellular Carcinoma, Stage III Childhood Hepatocellular Carcinoma, Stage IIIA Hepatocellular Carcinoma, Stage IIIB Hepatocellular Carcinoma, Stage IIIC Hepatocellular Carcinoma
- 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 group | Role | What they receive |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Patients 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.
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
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)
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.
- First posted26 Feb 2014 (estimated)
- Study start18 Nov 2013
- Primary completion19 Jul 2019
- Study completion19 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Adult Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Renuka Iyer, Principal investigator, Roswell Park Cancer Institute
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