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.
PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
Optional correlative studies
Optional correlative studies
Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Miller Children's Hospital
Long Beach, California, United States
Objective Response by RECIST Criteria v 1.1
Response rates will be calculated as the number of evaluable patients who are responders. Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 6 cycles (168 days)
Progression-free Survival According to RECIST Version 1.1
Percent probability of being progression free six months following enrollment. 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.
Time frame: Six months after enrollment
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity,
Each patient is classified as having experienced grade 3 or higher CTC version 4 toxicity if at any time during protocol therapy such an event is observed for the individual.
Time frame: six cycles of chemotherapy; expected to be 126 days of treatment
Pharmacokinetic (PK) Parameters of Sorafenib Tosylate
The trough sorafenib concentration is evaluated at baseline (prior to administration of Sorafenib) and 12 hours after administration of Sorafenib on day 15, day 56, day 112 and day 168 in micrograms/ml.
Time frame: Prior to administration of Sorafenib (baseline), day 15, day 56, day 112 and day 168
Change in VEGF and VEGFR-2
Serum VEGF and VEGF receptor 2 Concentration is evaluated at baseline and at day 15 of protocol therapy in picograms/ml.
Time frame: Prior to the administration of sorafenib (baseline) and day 15 of protocol therapy
Presence of BRAF Mutation or RET/PTC Rearrangement
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.
Time frame: At baseline
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Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Childrens Hospital of Orange County
Orange, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States
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