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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01502410




Registration number
NCT01502410
Ethics application status
Date submitted
29/12/2011
Date registered
30/12/2011
Date last updated
26/06/2018

Titles & IDs
Public title
Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer
Scientific 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 Papillary Thyroid Carcinoma
Secondary ID [1] 0 0
NCI-2012-00106
Secondary ID [2] 0 0
NCI-2012-00106
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Hepatocellular Carcinoma 0 0
Papillary Thyroid Cancer 0 0
Previously Treated Childhood Rhabdomyosarcoma 0 0
Recurrent Childhood Liver Cancer 0 0
Recurrent Childhood Rhabdomyosarcoma 0 0
Recurrent Thyroid Cancer 0 0
Recurrent Wilms Tumor and Other Childhood Kidney Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - sorafenib tosylate
Other interventions - pharmacological study
Other interventions - laboratory biomarker analysis

Experimental: 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

Experimental: 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

Experimental: 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

Experimental: 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


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

Other interventions: pharmacological study
Optional correlative studies

Other interventions: laboratory biomarker analysis
Optional correlative studies
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response by RECIST Criteria v 1.1
Timepoint [1] 0 0
6 cycles (168 days)
Secondary outcome [1] 0 0
Progression-free Survival According to RECIST Version 1.1
Timepoint [1] 0 0
Six months after enrollment
Secondary outcome [2] 0 0
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity,
Timepoint [2] 0 0
six cycles of chemotherapy; expected to be 126 days of treatment
Secondary outcome [3] 0 0
Pharmacokinetic (PK) Parameters of Sorafenib Tosylate
Timepoint [3] 0 0
Prior to administration of Sorafenib (baseline), day 15, day 56, day 112 and day 168
Secondary outcome [4] 0 0
Change in VEGF and VEGFR-2
Timepoint [4] 0 0
Prior to the administration of sorafenib (baseline) and day 15 of protocol therapy
Secondary outcome [5] 0 0
Presence of BRAF Mutation or RET/PTC Rearrangement
Timepoint [5] 0 0
At baseline

Eligibility
Key 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 age
2 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2014
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Canada
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British Columbia
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01502410
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AeRang Kim, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01502410