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

NCT ID: NCT01502410

Last Updated: 2018-06-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2014-06-30

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 Relapsed/Refractory Rhabdomyosarcoma

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

Group Type EXPERIMENTAL

sorafenib tosylate

Intervention Type DRUG

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

pharmacological study

Intervention Type OTHER

Optional correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Optional correlative studies

Group 2 Relapsed/Refractory Wilms tumor

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

Group Type EXPERIMENTAL

sorafenib tosylate

Intervention Type DRUG

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

pharmacological study

Intervention Type OTHER

Optional correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Optional correlative studies

Group 3 Relapsed/Refractory hepatocellular carcinoma

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

Group Type EXPERIMENTAL

sorafenib tosylate

Intervention Type DRUG

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

pharmacological study

Intervention Type OTHER

Optional correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Optional correlative studies

Group 4 Papillary thyroid carcinoma

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

Group Type EXPERIMENTAL

sorafenib tosylate

Intervention Type DRUG

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

pharmacological study

Intervention Type OTHER

Optional correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Optional correlative studies

Interventions

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sorafenib tosylate

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

Intervention Type DRUG

pharmacological study

Optional correlative studies

Intervention Type OTHER

laboratory biomarker analysis

Optional correlative studies

Intervention Type OTHER

Other Intervention Names

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BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN pharmacological studies

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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AeRang Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Miller Children's Hospital

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Childrens Hospital of Orange County

Orange, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Joseph Children's Hospital of Tampa

Tampa, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

University of Hawaii

Honolulu, Hawaii, United States

Site Status

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Southern Illinois University

Springfield, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Dana-Farber Harvard Cancer Center

Boston, Massachusetts, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

The Childrens Mercy Hospital

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Morristown Memorial Hospital

Morristown, New Jersey, United States

Site Status

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Oncology Group

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Greenville Cancer Treatment Center

Greenville, South Carolina, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Childrens Hospital-King's Daughters

Norfolk, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Sydney Children's Hospital

Randwick, New South Wales, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, Canada

Site Status

Countries

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United States Australia Canada

Other Identifiers

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NCI-2012-00106

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-ADVL1121

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000721611

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL1121

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL1121

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-00106

Identifier Type: -

Identifier Source: org_study_id

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