Clinical trial NCT01502410
Conditions: 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
Sponsor: National Cancer Institute (NCI)
Start date: 2012-01-01; Completion date: 2014-06-01
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Patients with relapsed or refractory rhabdomyosarcoma 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.

sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

pharmacological study: Optional correlative studies

laboratory biomarker analysis: Optional correlative studies arm 2: Patients with relapsed or refractory Wilms tumor 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.

sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

pharmacological study: Optional correlative studies

laboratory biomarker analysis: Optional correlative studies arm 3: Patients with relapsed or refractory hepatocellular carcinoma 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.

sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

pharmacological study: Optional correlative studies

laboratory biomarker analysis: Optional correlative studies arm 4: Patients with relapsed or refractory papillary thyroid carcinoma 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.

sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

pharmacological study: Optional correlative studies

laboratory biomarker analysis: Optional correlative studies
Interventions: intervention 1: sorafenib tosylate intervention 2: pharmacological study intervention 3: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 intervention 2: Optional correlative studies intervention 3: Optional correlative studies

Protocol documents: