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
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.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response by RECIST criteria v 1.1
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
Up to 5 years
No
AeRang Kim
Principal Investigator
Children's Oncology Group
United States: Food and Drug Administration
NCI-2012-00106
NCT01502410
January 2012
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Memorial Sloan Kettering Cancer Center | New York, New York 10021 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Mayo Clinic | Rochester, Minnesota 55905 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Medical City Dallas Hospital | Dallas, Texas 75230 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
Sinai Hospital of Baltimore | Baltimore, Maryland 21225 |
Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
Morristown Memorial Hospital | Morristown, New Jersey 07962-1956 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
Southern California Permanente Medical Group | Downey, California 90242 |
Children's Hospital Central California | Madera, California 93638-8762 |
Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Montefiore Medical Center | Bronx, New York 10467-2490 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
Lee Memorial Health System | Fort Myers, Florida 33902 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
Children's Hospital of Alabama | Birmingham, Alabama 35233 |
Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
University of North Carolina | Chapel Hill, North Carolina 27599 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
Wayne State University | Detroit, Michigan 48202 |
BI-LO Charities Children's Cancer Center | Greenville, South Carolina 29605 |
University of Texas Southwestern Medical Center | Dallas, Texas |
University of Kentucky | Lexington, Kentucky 40536-0098 |
Oregon Health and Science University | Portland, Oregon 97201 |
Tulane University Health Sciences Center | New Orleans, Louisiana 70112 |
Florida Hospital | Orlando, Florida 32803 |
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
Seattle Children's Hospital | Seattle, Washington 98105 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
Childrens Memorial Hospital | Chicago, Illinois 60614 |
University of Hawaii | Honolulu, Hawaii 96813 |
Saint John's Mercy Medical Center | Saint Louis, Missouri 63141 |
Columbia University Medical Center | New York, New York 10032 |
State University of New York Upstate Medical University | Syracuse, New York 13210 |
University of Illinois | Chicago, Illinois 60612 |
Cook Children's Medical Center | Fort Worth, Texas 76104 |
The Children's Medical Center of Dayton | Dayton, Ohio 45404 |
University of Minnesota Medical Center-Fairview | Minneapolis, Minnesota 55455 |
Children's Oncology Group | Arcadia, California 91006-3776 |
Southern Illinois University | Springfield, Illinois 62702 |
Riley Hospital for Children | Indianapolis, Indiana 46202 |
UMDNJ - Robert Wood Johnson University Hospital | New Brunswick, New Jersey 08903 |
Miller Children's Hospital | Long Beach, California 90806 |
Childrens Hospital of Orange County | Orange, California 92868-3874 |
Alfred I duPont Hospital for Children | Wilmington, Delaware 19803 |
Nemours Children's Clinic - Jacksonville | Jacksonville, Florida 32207-8426 |
Nemours Childrens Clinic - Orlando | Orlando, Florida 32806 |
Saint Joseph Children's Hospital of Tampa | Tampa, Florida 33607 |
Children's Healthcare of Atlanta - Egleston | Atlanta, Georgia 30322 |
The Childrens Mercy Hospital | Kansas City, Missouri 64108 |
Rainbow Babies and Childrens Hospital | Cleveland, Ohio 44106 |
East Tennessee Childrens Hospital | Knoxville, Tennessee 37916 |
Children's Hospital and Medical Center of Omaha | Omaha, Nebraska 68114 |
Childrens Hospital-King's Daughters | Norfolk, Virginia 23507 |
Dana-Farber Harvard Cancer Center | Boston, Massachusetts 02115 |
Mark O Hatfield-Warren Grant Magnuson Clinical Center | Bethesda, Maryland 20892 |
University of California San Francisco Medical Center-Parnassus | San Francisco, California 94143 |
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver, Colorado 80218 |
Greenville Cancer Treatment Center | Greenville, South Carolina 29605 |
Providence Sacred Heart Medical Center and Children's Hospital | Spokane, Washington 99204 |