Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
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.
Adult Primary Hepatocellular Carcinoma
Adult Primary Undifferentiated Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Childhood Hepatocellular Carcinoma
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Recurrent Childhood Liver Cancer
Stage C Adult Primary Liver Cancer (BCLC)
Stage D Adult Primary Liver Cancer (BCLC)
Stage III Childhood Liver Cancer
Stage IV Childhood Liver Cancer
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Granzyme B Production as a Biomarker for the Immunomodulatory Activity of Sorafenib in HCC|
- Overall survival (OS) [ Time Frame: Time between start of first treatment and death, assessed up to 6 months ] [ Designated as safety issue: No ]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.
- Granzyme B levels [ Time Frame: Up to day 35 ] [ Designated as safety issue: No ]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.
- Granzyme B level variations by presence of grade 3 or higher adverse events (AE), characterized using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) severity grade [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]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.
- Proportion of cluster of differentiation (CD)8+ T cells expressing granzyme B [ Time Frame: Up to day 35 ] [ Designated as safety issue: No ]
- Change in granzyme B levels after sorafenib tosylate treatment [ Time Frame: Baseline to up to 35 days ] [ Designated as safety issue: No ]The hypotheses of immediate (HI) and sustained improvement (HS) of immune function will be tested using a fixed-sequence procedure. Each hypothesis uses a permutation paired t-test with an upper 1-sided 0.05 significance threshold. HI considers a pGrzB increase between days 0 & ~28-35. If the HI test finds no short-term pGrzB improvement, the HS test will not be done. If HI indicates a short-time pGrzB improvement, HS considers a pGrzB increase between days 0 and 24 weeks (± 1 week). If both tests indicate improvements it will be concluded improved & sustained pGrzB response follows sorafenib.
|Study Start Date:||November 2013|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate)
Patients receive sorafenib tosylate PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Other Names:Other: laboratory biomarker analysis
I. 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.
I. 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.
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 and then periodically thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02072486
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Roswell Park 877-275-7724 ASKRPCI@roswellpark.org|
|Principal Investigator: Renuka V. Iyer|
|Principal Investigator:||Renuka Iyer||Roswell Park Cancer Institute|