Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer
This phase II trial studies how well sorafenib tosylate works in treating younger patients with relapsed or refractory rhabdomyosarcoma, Wilms tumor, liver cancer, or thyroid cancer. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Childhood Hepatocellular Carcinoma
Papillary Thyroid Cancer
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Liver Cancer
Recurrent Childhood Rhabdomyosarcoma
Recurrent Thyroid Cancer
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Drug: sorafenib tosylate
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib (IND# 69896) in Children and Young Adults With Relapsed/Refractory Rhabdomyosarcoma, Wilms Tumor, Hepatocellular Carcinoma, and Papillary Thyroid Carcinoma|
- Objective response by RECIST criteria v 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed according to the method of Chang
- Progression-free survival according to RECIST version 1.1 [ Time Frame: From date of enrollment to the date of disease progression, date of death, date of removal of all tumor by surgery or last patient contact, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]Progression-free interval (PFI) will be calculated as the date of enrollment until the end PFI date, where that date is calculated as the date of disease progression, date of death, date of removal of all tumors by surgery or last patient contact, whichever occurs first.
- Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Pharmacokinetic (PK) parameters of sorafenib tosylate [ Time Frame: At baseline, up to 12 hours and on day 15 of course 1, and prior to odd courses ] [ Designated as safety issue: No ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Change in VEGF and VEGFR-2 [ Time Frame: From baseline to day 15 of course 1 ] [ Designated as safety issue: No ]Descriptive statistics including mean, median, standard deviation, and range will be calculated for baseline and steady state VEGF and VEGFR-2. Changes from baseline to steady state on treatment with sorafenib will be evaluated using non-parametric paired tests if there is evidence of intra-patient correlation as assessed by Spearman's rank correlation.
- Presence of BRAF mutation or RET/PTC rearrangement [ Time Frame: At baseline ] [ Designated as safety issue: No ]Descriptive statistics including mean, median, standard deviation, and range will be calculated for baseline for patients with PTC, TG and TG antibody, and presence of BRAF mutation or RET/PTC rearrangement.
|Study Start Date:||January 2012|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate)
Patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Other Names:Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Optional correlative studies
I. To determine the objective response rate to sorafenib tosylate (sorafenib) in children with relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), or papillary thyroid carcinoma (PTC).
I. To further define and describe the toxicities of sorafenib administered on an oral, twice-daily continuous schedule.
II. To further characterize the pharmacokinetics of sorafenib in children with refractory cancer.
III. To estimate the progression-free survival on sorafenib for rhabdomyosarcoma, Wilms tumor, and hepatocellular carcinoma and compare to a group of patients enrolled on selected closed Phase II studies of Children Oncology Group (COG).
IV. To assess the biologic activity of sorafenib on vascular endothelial growth factor (VEGF) and soluble vascular endothelial growth factor receptor-2 (VEGFR-2) in peripheral blood samples. (Exploratory) V. To evaluate the presence of BRAF mutations and RET/PTC rearrangements in patients with PTC. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (rhabdomyosarcoma vs Wilms tumor vs hepatocellular carcinoma vs papillary thyroid carcinoma).
Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic studies, and VEGF and VEGFR-2 analysis by ELISA. Previously collected formalin-fixed paraffin-embedded tissue samples, from patients with papillary thyroid carcinoma, are also analyzed for BRAF mutation and RET/PTC rearrangements by PCR.
After completion of study treatment, patients are followed up for up to 5 years.