Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia
A Phase I/II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib (BAY 43-9006, NSC# 724772) in Children With Refractory Solid Tumors or Refractory Leukemias
8 other identifiers
interventional
70
2 countries
25
Brief Summary
This phase I/II trial is studying the side effects and best dose of sorafenib in treating young patients with relapsed or refractory solid tumors or leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2006
Longer than P75 for phase_1
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 30, 2006
CompletedFirst Submitted
Initial submission to the registry
September 30, 2011
CompletedFirst Posted
Study publicly available on registry
October 3, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 16, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 10, 2012
CompletedResults Posted
Study results publicly available
February 2, 2021
CompletedFebruary 2, 2021
January 1, 2021
5.8 years
September 30, 2011
February 25, 2020
January 13, 2021
Conditions
Outcome Measures
Primary Outcomes (12)
Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level
Number of patients with treatment-related dose limiting toxicities in cycle 1, as defined by study protocol, stratified by dose level.
Up to 28 days
Number of Patients With Treatment-related Adverse Events
Number of patients with treatment-related adverse events stratified by dose level through study completion.
Up to 2 years
Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
Area under the plasma concentration versus time curve (AUC) of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with refractory solid tumors or leukemias.
During cycle 1 or cycle 2 after at least 14 consecutive days of sorafenib administration Pre-dose, 0.5, 1, 2, 3, 5, 8 hours post dose
Clearance (Cl) of Sorafenib
Clearance of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with refractory solid tumors or leukemias.
During cycle 1 or cycle 2 after at least 14 consecutive days of sorafenib administration Pre-dose, 0.5, 1, 2, 3, 5, 8 hours post dose
Half-life of Sorafenib
Half-life of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with refractory solid tumors or leukemias.
During cycle 1 or cycle 2 after at least 14 consecutive days of sorafenib administration Pre-dose, 0.5, 1, 2, 3, 5, 8 hours post dose
Maximum Serum Concentration (Cmax) of Sorafenib
Maximum serum concentration (Cmax) of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with refractory solid tumors or leukemias.
During cycle 1 or cycle 2 after at least 14 consecutive days of sorafenib administration Pre-dose, 0.5, 1, 2, 3, 5, 8 hours post dose
Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level
Number of patients with treatment-related dose limiting toxicities in later cycles, as defined by study protocol, stratified by dose level.
Up to 2 years
Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
Area under the plasma concentration versus time curve (AUC) of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with AML and FLT3-ITD mutation.
8 hours post dose on day 1 of cycle 1
Clearance (Cl) of Sorafenib
Clearance of Sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with AML and FLT3-ITD mutation.
8 hours post dose on day 1 of cycle 1
Half-life of Sorafenib
Half-life of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with AML and FLT3-ITD mutation.
8 hours post dose on day 1 of cycle 1
Volume of Distribution at Steady State (Vss) of Sorafenib
Volume of distribution at steady state (Vss) of sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with refractory solid tumors, leukemia, or AML and FLT3-ITD mutation.
8 hours post dose on day 1 of cycle 1
Maximum Serum Concentration (Cmax) of Sorafenib
Maximum serum concentration (Cmax) of Sorefenib administered orally as tablets, BID approximately every 12 hours for cycles of 28 days with no rest period between cycles to children with AML and FLT3-ITD mutation.
8 hours post dose on day 1 of cycle 1
Secondary Outcomes (6)
Number of Patients Who Respond Using RECIST Criteria
Up to 2 years
Mean Concentration of VEGF2
28 days
Pharmacodynamics (PD) Blood Flow Part C
1 week prior to enrollment, then every 28 days
Number of Patients With DEMRI
Up to 2 years
Leukemia Mutations
1 week prior to enrollment
- +1 more secondary outcomes
Study Arms (1)
Treatment (sorafenib tosylate)
EXPERIMENTALPatients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given orally
Eligibility Criteria
You may qualify if:
- Diagnosis of 1 of the following:
- Histologically confirmed malignant solid tumor at original diagnosis or relapse
- Measurable or evaluable disease by CT scan or MRI
- Histologically confirmed leukemia, including 1 of the following:
- Acute lymphoblastic leukemia (ALL)
- Greater than 25% blasts in the bone marrow (M3 bone marrow)
- Acute myeloid leukemia (AML)
- Greater than 25% blasts in the bone marrow (M3 bone marrow)
- AML and FLT3-ITD mutation
- Patients must have ? 5% blasts in the bone marrow
- Active extramedullary disease (except leptomeningeal disease) allowed
- Juvenile myelomonocytic leukemia (JMML) meeting the following criteria:
- Peripheral blood monocytosis \> 1,000/mm\^3
- Blasts (including promonocytes) are \< 20% of the WBCs in the blood and of the nucleated bone marrow cells
- No Philadelphia chromosome (Ph) or BCR/ABL fusion gene
- +79 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Brigitte C Widemann
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 30, 2011
First Posted
October 3, 2011
Study Start
May 30, 2006
Primary Completion
March 16, 2012
Study Completion
December 10, 2012
Last Updated
February 2, 2021
Results First Posted
February 2, 2021
Record last verified: 2021-01