Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

• Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:

• Rhabdomyosarcoma (RMS)

• Wilms tumor

• Hepatocellular carcinoma (HCC)

• Papillary thyroid carcinoma (PTC)

• Patients must have relapsed or refractory disease (RMS, Wilms tumor, HCC, PTC)

• Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)

• The following do not qualify as measurable disease:

• Malignant fluid collections (e.g., ascites, pleural effusions)

• Bone marrow infiltration

• Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography [PET] scans)

• Elevated tumor markers in plasma or cerebrospinal fluid(CSF)

• Previously radiated lesions that have not demonstrated clear progression post radiation

• Leptomeningeal lesions that do not meet the requirements noted above

• Patients with HCC must be relapsed or refractory to conventional chemotherapy

• Patients with PTC must be refractory to radioactive iodine (RAI)

• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

• Patients with known metastasis to the brain will be excluded from trial participation unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months

• Rhabdomyosarcoma and Wilms strata: patients must be ≥ 24 months and ≤ 30 years of age at study enrollment

• Hepatocellular carcinoma (HCC): patients must be ≥ 24 months and < 18 years of age at study enrollment

• Papillary thyroid carcinoma (PTC): patients must be ≥ 24 months and ≤ 21 years of age at study enrollment

• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories 0, 1, or 2

• Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age

• Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

• Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

• Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)

• Hemoglobin 8.0 g/dL (may receive red blood cell[RBC] transfusions)

• Creatinine clearance or radioisotope glomerular filtration rate(GFR) 70 mL/min OR a serum creatinine based on age/gender as follows:

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

• SGPT (ALT) ≤ 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

• PT, PTT, and INR < 1.5 times ULN

• Normal serum lipase and amylase (per institutional normal values)

• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination

• A blood pressure (BP) ≤ the 95^th percentile for age, height, and gender; and not receiving medication for treatment of hypertension

• Patients who are pregnant or breast-feeding are not eligible

• Negative pregnancy tests must be obtained in girls who are post-menarchal

• Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug

• Patients with clinical symptoms of hepatic encephalopathy or ascites are not eligible

• Patients who have an uncontrolled infection are not eligible

• Patients with evidence of bleeding diathesis are not eligible

• Patients with known Gilbert syndrome are not eligible

• Patients who, in the opinion of the investigator, may not be able to comply with the safety-monitoring requirements of the study are not eligible

• No concurrent chemotherapy, radiation therapy, immunomodulating agents, or other investigational agents

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

• Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)

• At least 7 days must have elapsed since the completion of therapy with a growth factor (at least 14 days must have elapsed after receiving pegfilgrastim)

• At least 7 days must have elapsed since completion of therapy with a biologic agent;

• For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur

• At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody

• At least 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given

• No evidence of active graft-vs-host disease and ≥ 2 months must have elapsed since transplant (stem cell transplant or rescue without total-body irradiation)

• For patients with papillary thyroid carcinoma (PTC) only: ≥ 3 weeks from prior radioiodine (RAI) treatment

• Patients requiring corticosteroids that have not been on a stable or decreasing dose of corticosteroid for 7 days prior to enrollment are not eligible

• Patients who are currently receiving another investigational drug are not eligible

• Patients who are currently receiving other anti-cancer agents are not eligible

• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial

• Patients who take cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, grapefruit juice, or St. Johns wort will not be eligible for the trial

• Patients who have received prior treatment with sorafenib are not eligible

• Patients must not be on therapeutic anti-coagulation;

• Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial devices is allowed provided that the requirements for prothrombin time(PT), partial thromboplastin time(PTT), and international normalized ratio(INR) are met

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

AeRang Kim

Principal Investigator

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Alyssa T Reddy	Ph: 205-934-0309
	UAB Comprehensive Cancer Center
		Alyssa T Reddy	Ph: 205-934-0309
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		David L Becton	Ph: 501-364-7373
California
	Arcadia
	Children's Oncology Group
		AeRang Kim	Ph: 202-476-2800
			Email: aekim@cnmc.org
	Downey
	Southern California Permanente Medical Group
		Robert M Cooper	Ph: 626-564-3455
	Long Beach
	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
		Amanda M Termuhlen	Ph: 562-933-5437
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph: 323-361-4110
	Madera
	Children's Hospital Central California
		Vonda L Crouse	Ph: 866-353-5437
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-997-3000
	San Diego
	Rady Children's Hospital - San Diego
		William D Roberts	Ph: 858-966-5934
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Steven G DuBois	Ph: 877-827-3222
Colorado
	Denver
	Presbyterian - St. Luke's Medical Center
		Jennifer J Clark	Ph: 866-775-6246
Connecticut
	Hartford
	Connecticut Children's Medical Center
		Michael S Isakoff	Ph: 860-545-9981
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Christopher N Frantz	Ph: 302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Jeffrey S Dome	Ph: 202-884-2549
Florida
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Emad K Salman	Ph: 239-343-5333
	Jacksonville
	Nemours Children's Clinic
		Eric S Sandler	Ph: 904-697-3529
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clifford A Selsky	Ph: 407-303-5623
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph: 407-650-7150
	Pensacola
	Nemours Children's Clinic - Pensacola
		Jeffrey H Schwartz	Ph: 904-697-3529
	Saint Petersburg
	All Children's Hospital
		Gregory A Hale	Ph: 727-767-2423
			Email: HamblinF@allkids.org
	Tampa
	St. Joseph's Children's Hospital of Tampa
		Hardeo K Panchoosingh	Ph: 800-882-4123
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard M Katzenstein	Ph: 888-785-1112
Hawaii
	Honolulu
	Cancer Research Center of Hawaii
		Robert W Wilkinson	Ph: 808-983-6090
Illinois
	Chicago
	Ann and Robert H. Lurie Children's Hospital of Chicago
		David O Walterhouse	Ph: 773-880-4562
	University of Chicago Cancer Research Center
		Susan L Cohn	Ph: 773-834-7424
	University of Illinois Cancer Center
		Mary L Schmidt	Ph: 312-355-3046
	Peoria
	Saint Jude Midwest Affiliate
		Pedro A De Alarcon	Ph: 309-655-3258
	Springfield
	Simmons Cooper Cancer Institute
		Gregory P Brandt	Ph: 217-545-7929
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		Robert J Fallon	Ph: 317-274-2552
Kentucky
	Lexington
	University of Kentucky Chandler Medical Center
		Martha F Greenwood	Ph: 859-257-3379
	Louisville
	Kosair Children's Hospital
		Salvatore J Bertolone	Ph: 866-530-5516
Louisiana
	New Orleans
	Tulane Cancer Center at Tulane University Hospital and Clinic
		Tammuella C Singleton	Ph: 504-988-6121
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Joseph M Wiley	Ph: 410-601-6120
			Email: pridgely@lifebridgehealth.org
	Bethesda
	NIH - Warren Grant Magnuson Clinical Center
		Brigitte C. Widemann	Ph: 800-411-1222
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Carlos Rodriguez-Galindo	Ph: 612-624-8651
			Email: carlos.rodriguez-galindo@dfci.harvard.edu
		Carlos Rodriguez-Galindo	Ph: 866-790-4500
Michigan
	Detroit
	Wayne State University
		Zhihong J Wang	Ph: 313-576-9363
	Kalamazoo
	Bronson Methodist Hospital
		Jeffrey S Lobel	Ph: 800-227-2345
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Brenda J Weigel	Ph: 612-624-2620
	Rochester
	Mayo Clinic Cancer Center
		Carola A. S. Arndt	Ph: 507-538-7623
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail C Megason	Ph: 601-815-6700
Missouri
	Kansas City
	Children's Mercy Hospital
		Kathleen A Neville	Ph: 816-234-3265
	Saint Louis
	David C. Pratt Cancer Center at St. John's Mercy
		Bethany G. Sleckman	Ph: 913-948-5588
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Robert J Hayashi	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
Nebraska
	Omaha
	Children's Hospital
		Minnie Abromowitch	Ph: 402-955-3949
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Burton E Appel	Ph: 201-996-2879
	Morristown
	Carol G. Simon Cancer Center at Morristown Memorial Hospital
		Steven L Halpern	Ph: 973-971-5900
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Richard A Drachtman	Ph: 732-235-8675
	Summit
	Overlook Hospital
		Steven L Halpern	Ph: 973-971-5900
New Mexico
	Albuquerque
	University of New Mexico Cancer Center
		Koh B Boayue	Ph: 505-272-6972
New York
	Bronx
	Montefiore Medical Center
		Rosanna J Ricafort	Ph: 718-904-2730
			Email: aecc@aecom.yu.edu
	Buffalo
	Roswell Park Cancer Institute
		Martin L Brecher	Ph: 877-275-7724
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Alice Lee	Ph: 212-305-8615
	Memorial Sloan-Kettering Cancer Center
		Peter G Steinherz	Ph: 212-639-7202
	Syracuse
	SUNY Upstate Medical University Hospital
		Karol H Kerr	Ph: 315-464-5476
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Stuart H Gold	Ph: 877-668-0683
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Joel A Kaplan	Ph: 704-355-2884
	Presbyterian Cancer Center at Presbyterian Hospital
		Paulette C Bryant	Ph: 704-384-5369
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Thomas W McLean	Ph: 336-713-6771
Ohio
	Akron
	Akron Children's Hospital
		Steven J Kuerbitz	Ph: 330-543-3193
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John P Perentesis	Ph: 513-636-2799
	Cleveland
	Seidman Cancer Center at University Hospitals/Case Medical Center
		Yousif (Joe) H Matloub	Ph: 216-844-5437
	Columbus
	Nationwide Children's Hospital
		Mark A Ranalli	Ph: 614-722-2708
	Dayton
	Dayton Children's - Dayton
		Emmett H Broxson	Ph: 800-228-4055
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Linda C. Stork	Ph: 503-494-1080
			Email: trials@ohsu.edu
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		Frank M Balis	Ph: 215-590-2810
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Arthur K Ritchey	Ph: 412-692-5573
South Carolina
	Greenville
	BI-LO Charities Children's Cancer Center
		Nichole L Bryant	Ph: 864-241-6251
Tennessee
	Knoxville
	East Tennessee Children's Hospital
		Ray C Pais	Ph: 865-541-8266
	Nashville
	Vanderbilt-Ingram Cancer Center
		Scott C Borinstein	Ph: 800-811-8480
Texas
	Corpus Christi
	Driscoll Children's Hospital
		M. C Johnson	Ph: 361-694-5311
	Dallas
	Medical City Dallas Hospital
		Carl Lenarsky	Ph: 972-566-5588
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Naomi J Winick	Ph: 214-648-7097
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Mary Meaghan P Granger	Ph: 682-885-2103
	Houston
	Dan L. Duncan Cancer Center at Baylor College of Medicine
		Lisa R Bomgaars	Ph: 713-798-1354
			Email: burton@bcm.edu
Virginia
	Norfolk
	Children's Hospital of The King's Daughters
		Eric J Lowe	Ph: 757-668-7243
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie R Park	Ph: 866-987-2000
	Spokane
	Providence Cancer Center at Sacred Heart Medical Center
		Judy L Felgenhauer	Ph: 800-228-6618
			Email: HopeBeginsHere@providence.org
Wisconsin
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael E Kelly	Ph: 414-805-4380
Australia
New South Wales
	Randwick
	Sydney Children's Hospital
		Draga Barbaric	Ph: (02) 9382-1721
Western Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine H Cole	Ph: (08) 9340 8330
			Email: admin@childcancerresearch.com.au
Canada
British Columbia
	Vancouver
	Children's and Women's Hospital of British Columbia
		Caron Strahlendorf	Ph: 604-875-2345ext6477
Nova Scotia
	Halifax
	IWK Health Centre
		Margaret C Yhap	Ph: 902-470-8394
Ontario
	Hamilton
	McMaster Children's Hospital at Hamilton Health Sciences
		Carol Portwine	Ph: 905-521-2100ext74595
	Toronto
	Hospital for Sick Children
		Ronald M Grant	Ph: 416-813-7654ext2027
			Email: jason.mcguire@sickkids.ca
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph: 514-345-4931
	Montreal Children's Hospital at McGill University Health Center
		Sharon B Abish	Ph: 514-412-4445
			Email: info@thechildren.com

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01502410
Information obtained from ClinicalTrials.gov on December 05, 2012

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