Clinical Trial: Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib in Children and Young Adults With Relapsed/Refractory Rhabdomyosarcoma, Wilms Tumor, Hepatocellular Carcinoma, and P

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 Summary:

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 pharmacoki
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective Response by RECIST Criteria v 1.1 [ Time Frame: 6 cycles (168 days) ]

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.


Original Primary Outcome: Objective Response by RECIST Criteria v 1.1

Current Secondary Outcome:

  • 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 ]
    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 ]
  • 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 ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • Toxicity
  • Progression-free survival
  • Pharmacokinetic parameters of sorafenib tosylate


Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 29, 2011
Date Started: January 2012
Date Completion:
Last Updated: May 14, 2015
Last Verified: May 2015