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Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01445080
Collaborator
(none)
70
Enrollment
25
Locations
1
Arm
78.4
Actual Duration (Months)
2.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Drug: Sorafenib Tosylate
 Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

  1. Determine the maximum-tolerated dose (MTD) and recommended phase II dose of sorafenib in pediatric patients with relapsed or refractory solid tumors.

  2. Determine whether pediatric patients with relapsed or refractory leukemia can tolerate the MTD of sorafenib for solid tumors.

  3. Determine the tolerability, active N-oxide metabolite, pharmacodynamics, and activity of sorafenib a the MTD in a subset of patients with acute myeloid leukemia (AML) and FLT3-ITD mutation.

  4. Determine the toxicities of this drug in these patients. V. Determine the pharmacokinetics of this drug in these patients.

SECONDARY OBJECTIVES:

  1. Determine, preliminarily, the antitumor activity of this drug within the confines of a phase I trial.

  2. Assess the biologic effect of sorafenib on circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF, and VEGF-2 in peripheral blood.

  3. Assess the gene expression, proteomic profile, and ERK phosphorylation in blasts of patients with refractory leukemia treated with this regimen.

  4. Assess the effect of sorafenib on solid tumor vascularity and tumor blood flow using dynamic contrast-enhanced MRI (DEMRI) in patients with measurable soft tissue tumors.

  5. Analyze tumor samples and leukemic blasts for the presence of ras, raf, or FLT3 (leukemias) mutations.

  6. Analyze the plasma inhibitory activity for FLT3 phosphorylation in peripheral blood of patients with AML and FLT3-ITD mutation.

  7. Determine the tolerability, pharmacokinetics of sorafenib and sorafenib?s active N-oxide metabolite, pharmacodynamics, and activity of sorafenib administered at the MTD for refractory leukemias in a subset of patients with AML and FLT3-ITD mutation.

  8. Analyze the plasma inhibitory activity for FLT3 phosphorylation in peripheral blood samples obtained at the time of PK studies in patients with FLT3-ITD mutation AML.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (malignant solid tumor vs leukemia).

STRATUM I(REFRACTORY SOLID TUMOR PATIENTS): Patients 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. Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Once the MTD is determined, up to 6 additional patients under 12 years of age may be treated at the MTD. The MTD dose level is also expanded to enroll up to 6 patients with refractory leukemia.

STRATUM II (REFRACTORY LEUKEMIA PATIENTS): A cohort of 3-6 patients with leukemia receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience DLT during course 1 of treatment.

STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION PATIENTS): Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.

After completion of study treatment, patients are followed periodically.

Study Design

Study Type:
Interventional
Actual Enrollment :
70 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 30, 2006
Actual Primary Completion Date :
Mar 16, 2012
Actual Study Completion Date :
Dec 10, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (sorafenib tosylate)

Patients 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.

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Drug: Sorafenib Tosylate
Given orally
Other Names:
  • BAY 43-9006 Tosylate
  • BAY 54-9085
  • Nexavar
  • sorafenib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level [Up to 28 days]

      Number of patients with treatment-related dose limiting toxicities in cycle 1, as defined by study protocol, stratified by dose level.

    2. Number of Patients With Treatment-related Adverse Events [Up to 2 years]

      Number of patients with treatment-related adverse events stratified by dose level through study completion.

    3. Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib [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]

      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.

    4. Clearance (Cl) of Sorafenib [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 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.

    5. Half-life of Sorafenib [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 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.

    6. Maximum Serum Concentration (Cmax) of Sorafenib [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 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.

    7. Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level [Up to 2 years]

      Number of patients with treatment-related dose limiting toxicities in later cycles, as defined by study protocol, stratified by dose level.

    8. Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib [8 hours post dose on day 1 of cycle 1]

      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.

    9. Clearance (Cl) of Sorafenib [8 hours post dose on day 1 of cycle 1]

      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.

    10. Half-life of Sorafenib [8 hours post dose on day 1 of cycle 1]

      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.

    11. Volume of Distribution at Steady State (Vss) of Sorafenib [8 hours post dose on day 1 of cycle 1]

      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.

    12. Maximum Serum Concentration (Cmax) of Sorafenib [8 hours post dose on day 1 of cycle 1]

      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.

    Secondary Outcome Measures

    1. Number of Patients Who Respond Using RECIST Criteria [Up to 2 years]

      Frequency (%) of patients with Partial Response (PR) or Complete Response (CR) using the RECIST criteria by study part and dose level

    2. Mean Concentration of VEGF2 [28 days]

      Mean concentration of VEGF2 in peripheral blood sample.

    3. Pharmacodynamics (PD) Blood Flow Part C [1 week prior to enrollment, then every 28 days]

      Pharmacodynamics: tumor blood flow in patients with AML and FLT3-ITD mutation using dynamic contrast enhanced MRI (DEMRI) (Part C).

    4. Number of Patients With DEMRI [Up to 2 years]

      Assess effect on tumor blood flow via DEMRI in patients with measurable soft tissue tumors.

    5. Leukemia Mutations [1 week prior to enrollment]

      Analyze tumor samples and leukemic blasts from patients entered on this study for the presence of ras, raf, or FLT3 (leukemia) mutations.

    6. Plasma Inhibitory Activity (PIA) [1 week prior to enrollment and then every 28 days]

      Analyze the plasma inhibitory activity (PIA) for FLT3 phosphorylation in peripheral blood samples obtained at the time of PK studies in patients with FLT3-ITD mutation AML (Part C).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    • Has ? 2 of the following additional diagnostic criteria:

    • Hemoglobin F increased for age

    • Immature granulocytes in the peripheral blood

    • WBC > 10,000/mm^3

    • Clonal chromosomal abnormality (e.g., may be monosomy 7)

    • Sargramostim (GM-CSF) hypersensitivity of myeloid progenitors in vitro

    • Chronic myelogenous leukemia (CML) in blast crisis

    • Greater than 25% blasts in the bone marrow (M3 bone marrow)

    • Patients with Ph-positive CML must be refractory to imatinib mesylate

    • Relapsed or refractory disease

    • Patients with acute promyelocytic leukemia (APL) must be refractory to treatment with tretinoin and arsenic trioxide

    • Standard curative therapies or therapies proven to prolong survival with an acceptable quality of life do not exist

    • Active extramedullary disease, except active leptomeningeal leukemia, allowed

    • No brain tumors or known brain metastases

    • Karnofsky performance status (PS) 50-100% (for patients > 10 years of age)

    • Lansky PS 50-100% (for patients ? 10 years of age)

    • Patients with solid tumors must have adequate bone marrow function, as defined by the following:

    • Absolute neutrophil count ? 1,000/mm^3

    • Platelet count ? 75,000/mm^3 (transfusion independent)

    • Hemoglobin ? 8.0 g/dL (red blood cell [RBC] transfusions allowed)

    • Patients with leukemia may have abnormal blood counts but must meet the following criteria:

    • Platelet count ? 20,000/mm^3 (platelet transfusions allowed)

    • Hemoglobin ? 8.0 g/L (RBC transfusions allowed)

    • Patients with acute myeloid leukemia and FLT3-ITD mutation

    • Platelet count ? 20,000/mm^3

    • Lipase and amylase normal

    • Creatinine clearance or radioisotope glomerular filtration rate ? 70 mL/min OR creatinine normal based on age as follows:

    • No greater than 0.8 mg/dL (for patients 5 years of age and under)

    • No greater than 1.0 mg/dL (for patients 6-10 years of age)

    • No greater than 1.2 mg/dL (for patients 11-15 years of age)

    • No greater than 1.5 mg/dL (for patients over 15 years of age)

    • Patients with solid tumors must meet the following criteria:

    • Bilirubin normal for age

    • ALT normal for age (for the purpose of this study, the upper limit of normal [ULN] for ALT is 45 ?/L)

    • Serum albumin ? 2 g/dL

    • Patients with leukemia must meet the following criteria:

    • Bilirubin (sum of conjugated + unconjugated) ? 1.5 times ULN for age

    • ALT ? 5.0 times ULN for age (? 225 ?/L) (for the purpose of this study, the ULN for ALT is 45 ?/L)

    • Serum albumin ? 2 g/dL

    • Albumin ? 2 g/dL

    • PT, PTT, and INR normal (for patients on prophylactic anticoagulation)

    • No evidence of dyspnea at rest

    • No exercise intolerance

    • Pulse oximetry >94% on room air, if there is clinical indication for determination

    • Diastolic blood pressure ? the 95th percentile for age and gender (height included for AML and FLT3-ITD mutation patients)

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • No uncontrolled infection

    • Able to swallow tablets

    • No evidence of bleeding diathesis

    • No other medical condition or situation that would preclude study compliance

    • No known Gilbert syndrome

    • Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy (for patients with solid tumors)

    • Recovered from the non-hematologic toxic effects of all prior therapy (for patients with leukemia)

    • Recovered from acute non-hematologic toxic effects of all prior anti-cancer chemotherapy (for patients with AML and FLT3-ITD mutation)

    • At least 7 days since prior hematopoietic growth factors

    • At least 7 days since prior biologic agents

    • At least 2 weeks since prior local palliative radiotherapy (small port)

    • At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiation to ? 50% of the pelvis

    • At least 6 weeks since other prior substantial bone marrow radiation (e.g., skull, spine, pelvis, ribs)

    • At least 3 months since prior stem cell transplantation or rescue (for patients with solid tumors)

    • No evidence of active graft-vs-host disease

    • At least 3 months since prior myeloablative therapy followed by bone marrow or stem cell transplantation (for patients with leukemia)

    • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) (for patients with solid tumors)

    • At least 24 hours since prior nitrosoureas (for patients with AML and FLT3-ITD mutation)

    • At least 2 weeks since prior chemotherapy (for patients with leukemia)

    • At least 3 weeks since prior monoclonal antibody therapy

    • No prior sorafenib

    • No other concurrent investigational drugs

    • No other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy

    • Concurrent maintenance-like chemotherapy for patients with AML and FLT3-ITD mutation allowed

    • No concurrent administration of any of the following:

    • Cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)

    • Rifampin

    • Grapefruit juice

    • Hypericum perforatum (St. John wort)

    • No concurrent therapeutic anticoagulation

    • Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR, or PTT are met

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 Children's Hospital of Orange County Orange California United States 92868
    3 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    4 Children's National Medical Center Washington District of Columbia United States 20010
    5 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    6 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    7 Riley Hospital for Children Indianapolis Indiana United States 46202
    8 National Institutes of Health Clinical Center Bethesda Maryland United States 20892
    9 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    10 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    11 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    12 Washington University School of Medicine Saint Louis Missouri United States 63110
    13 Columbia University/Herbert Irving Cancer Center New York New York United States 10032
    14 State University of New York Upstate Medical University Syracuse New York United States 13210
    15 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    16 Oregon Health and Science University Portland Oregon United States 97239
    17 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    18 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    19 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    20 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    21 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    22 Seattle Children's Hospital Seattle Washington United States 98105
    23 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    24 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    25 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Brigitte C Widemann, COG Phase I Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01445080
    Other Study ID Numbers:
    • NCI-2009-00358
    • NCI-2009-00358
    • 06-C-0233
    • CDR0000483040
    • COG-ADVL0413
    • NCI-06-C-0233
    • 060233
    • ADVL0413
    • ADVL0413
    • ADVL0413
    • U01CA097452
    • NCT00343694
    • NCT01648413
    First Posted:
    Oct 3, 2011
    Last Update Posted:
    Feb 2, 2021
    Last Verified:
    Jan 1, 2021
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Leukemia, Promyelocytic, Acute
    Leukemia, Myelomonocytic, Juvenile
    Recurrence
    Philadelphia Chromosome
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Period Title: Overall Study
    STARTED 7 5 12 8 4 9 2 5 18
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 7 5 12 8 4 9 2 5 18

    Baseline Characteristics

    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2 Total
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours Patients receive oral sorafenib 130 mg/m^2 every 12 hours Patients receive oral sorafenib 150 mg/m^2 every 12 hours Patients receive oral sorafenib 200 mg/m^2 every 12 hours Patients receive oral sorafenib 250 mg/m^2 every 12 hours Patients receive oral sorafenib 150 mg/m^2 every 12 hours Patients receive oral sorafenib 200 mg/m^2 every 12 hours Patients receive oral sorafenib 150 mg/m^2 every 12 hours Patients receive oral sorafenib 200 mg/m^2 every 12 hours Total of all reporting groups
    Overall Participants 7 5 12 8 4 9 2 5 18 70
    Age (Count of Participants)
    <=18 years
    4
    57.1%
    5
    100%
    11
    91.7%
    6
    75%
    4
    100%
    8
    88.9%
    2
    100%
    5
    100%
    15
    83.3%
    60
    85.7%
    Between 18 and 65 years
    3
    42.9%
    0
    0%
    1
    8.3%
    2
    25%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    3
    16.7%
    10
    14.3%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    17
    16
    13.5
    13.5
    11.5
    13
    10.5
    12
    14.5
    14
    Sex: Female, Male (Count of Participants)
    Female
    4
    57.1%
    1
    20%
    9
    75%
    3
    37.5%
    1
    25%
    1
    11.1%
    0
    0%
    0
    0%
    4
    22.2%
    23
    32.9%
    Male
    3
    42.9%
    4
    80%
    3
    25%
    5
    62.5%
    3
    75%
    8
    88.9%
    2
    100%
    5
    100%
    14
    77.8%
    47
    67.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    14.3%
    1
    20%
    3
    25%
    0
    0%
    2
    50%
    1
    11.1%
    0
    0%
    1
    20%
    2
    11.1%
    11
    15.7%
    Not Hispanic or Latino
    5
    71.4%
    4
    80%
    8
    66.7%
    8
    100%
    1
    25%
    8
    88.9%
    2
    100%
    4
    80%
    16
    88.9%
    56
    80%
    Unknown or Not Reported
    1
    14.3%
    0
    0%
    1
    8.3%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    4.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    Asian
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    50%
    1
    20%
    0
    0%
    4
    5.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    20%
    0
    0%
    3
    37.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    16.7%
    7
    10%
    White
    6
    85.7%
    2
    40%
    10
    83.3%
    5
    62.5%
    2
    50%
    8
    88.9%
    1
    50%
    3
    60%
    15
    83.3%
    52
    74.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    14.3%
    1
    20%
    2
    16.7%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    6
    8.6%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level
    Description Number of patients with treatment-related dose limiting toxicities in cycle 1, as defined by study protocol, stratified by dose level.
    Time Frame Up to 28 days

    Outcome Measure Data

    Analysis Population Description
    There were 55 evaluable patients.
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 6 3 12 7 2 6 2 5 12
    Count of Participants [Participants]
    0
    0%
    0
    0%
    5
    41.7%
    1
    12.5%
    2
    50%
    0
    0%
    2
    100%
    0
    0%
    3
    16.7%
    2. Primary Outcome
    Title Number of Patients With Treatment-related Adverse Events
    Description Number of patients with treatment-related adverse events stratified by dose level through study completion.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    There were 55 evaluable patients.
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 7 5 12 8 4 9 2 5 18
    Count of Participants [Participants]
    6
    85.7%
    3
    60%
    12
    100%
    7
    87.5%
    2
    50%
    6
    66.7%
    2
    100%
    5
    100%
    12
    66.7%
    3. Primary Outcome
    Title Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) studies were completed for stratums I and II. Summary statistics for PK analysis was performed regardless of dose level as pre-specified in the protocol. PK was not performed in stratum III
    Arm/Group Title STRATUM I (REFRACTORY SOLID TUMOR) STRATUM II (REFRACTORY LEUKEMIA)
    Arm/Group Description Patients 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. Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Once the MTD is determined, up to 6 additional patients under 12 years of age may be treated at the MTD. The MTD dose level is also expanded to enroll up to 6 patients with refractory leukemia. A cohort of 3-6 patients with leukemia receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience DLT during course 1 of treatment
    Measure Participants 29 5
    Mean (Full Range) [µg•h/ml]
    38.66
    50.03
    4. Primary Outcome
    Title Clearance (Cl) of Sorafenib
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) studies were completed for stratums I and II. Summary statistics for PK analysis was performed regardless of dose level as pre-specified in the protocol. PK was not performed in stratum III
    Arm/Group Title STARTUM I (REFRACTORY SOLID TUMORS) STRATUM II (REFRACTORY LEUKEMIA)
    Arm/Group Description Patients 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. Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Once the MTD is determined, up to 6 additional patients under 12 years of age may be treated at the MTD. The MTD dose level is also expanded to enroll up to 6 patients with refractory leukemia. A cohort of 3-6 patients with leukemia receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience DLT during course 1 of treatment.
    Measure Participants 13 4
    Mean (Full Range) [mL/min/m^2]
    57.2
    72.6
    5. Primary Outcome
    Title Half-life of Sorafenib
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM I (REFRACTORY SOLID TUMOR STRATUM II (REFRACTORY LEUKEMIA)
    Arm/Group Description Patients 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. Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Once the MTD is determined, up to 6 additional patients under 12 years of age may be treated at the MTD. The MTD dose level is also expanded to enroll up to 6 patients with refractory leukemia. A cohort of 3-6 patients with leukemia receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience DLT during course 1 of treatment
    Measure Participants 0 0
    6. Primary Outcome
    Title Maximum Serum Concentration (Cmax) of Sorafenib
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for patients from Part A:130 mg/m^2
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 4 9 4 1 4 1 11
    Mean (Standard Error) [µg/ml]
    0.71
    (0.53)
    1.88
    (1.55)
    1.98
    (1.25)
    1.80
    (0)
    5.97
    (4.45)
    5.02
    (0)
    7.95
    (.43)
    7. Primary Outcome
    Title Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level
    Description Number of patients with treatment-related dose limiting toxicities in later cycles, as defined by study protocol, stratified by dose level.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    There were 55 evaluable patients
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 6 3 12 7 2 6 2 5 12
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    8.3%
    1
    12.5%
    1
    25%
    1
    11.1%
    0
    0%
    0
    0%
    2
    11.1%
    8. Primary Outcome
    Title Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
    Description 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.
    Time Frame 8 hours post dose on day 1 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION)
    Arm/Group Description Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.
    Measure Participants 0
    9. Primary Outcome
    Title Clearance (Cl) of Sorafenib
    Description 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.
    Time Frame 8 hours post dose on day 1 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION)
    Arm/Group Description Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.
    Measure Participants 0
    10. Primary Outcome
    Title Half-life of Sorafenib
    Description 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.
    Time Frame 8 hours post dose on day 1 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION)
    Arm/Group Description Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.
    Measure Participants 0
    11. Primary Outcome
    Title Volume of Distribution at Steady State (Vss) of Sorafenib
    Description 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.
    Time Frame 8 hours post dose on day 1 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM I (REFRACTORY SOLID TUMOR STRATUM II (REFRACTORY LEUKEMIA) STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION)
    Arm/Group Description Patients 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. Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Once the MTD is determined, up to 6 additional patients under 12 years of age may be treated at the MTD. The MTD dose level is also expanded to enroll up to 6 patients with refractory leukemia. A cohort of 3-6 patients with leukemia receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience DLT during course 1 of treatment Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.
    Measure Participants 0 0 0
    12. Primary Outcome
    Title Maximum Serum Concentration (Cmax) of Sorafenib
    Description 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.
    Time Frame 8 hours post dose on day 1 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    Data was and never will be collected
    Arm/Group Title STRATUM III (ACUTE MYELOID LEUKEMIA AND FLT3-ITD MUTATION)
    Arm/Group Description Patients receive sorafenib as in stratum 1 at the MTD determined in stratum 2. Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3 phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras, raf, or FLT3.
    Measure Participants 0
    13. Secondary Outcome
    Title Number of Patients Who Respond Using RECIST Criteria
    Description Frequency (%) of patients with Partial Response (PR) or Complete Response (CR) using the RECIST criteria by study part and dose level
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    There were 55 evaluable patients
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 6 3 12 7 2 6 2 5 12
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    4
    80%
    0
    0%
    14. Secondary Outcome
    Title Mean Concentration of VEGF2
    Description Mean concentration of VEGF2 in peripheral blood sample.
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Data were not collected for Part A: 250 mg/m^2, Part B:150 mg/m^2, Part B: 200 mg/m^2, and Part C:150 mg/m^2
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 4 2 5 3 4
    Mean (Standard Deviation) [cells/ml]
    2650
    (2243.49)
    247.5
    (258.09)
    3531.5
    (4775.11)
    430
    (324.50)
    100
    (124.90)
    15. Secondary Outcome
    Title Pharmacodynamics (PD) Blood Flow Part C
    Description Pharmacodynamics: tumor blood flow in patients with AML and FLT3-ITD mutation using dynamic contrast enhanced MRI (DEMRI) (Part C).
    Time Frame 1 week prior to enrollment, then every 28 days

    Outcome Measure Data

    Analysis Population Description
    This data were not and will never be collected
    Arm/Group Title Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 150 mg/m^2 every 12 hours.
    Measure Participants 0
    16. Secondary Outcome
    Title Number of Patients With DEMRI
    Description Assess effect on tumor blood flow via DEMRI in patients with measurable soft tissue tumors.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    There were 55 evaluable patients
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours. Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    Measure Participants 6 3 12 7 2 6 2 5 12
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    1
    12.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    17. Secondary Outcome
    Title Leukemia Mutations
    Description Analyze tumor samples and leukemic blasts from patients entered on this study for the presence of ras, raf, or FLT3 (leukemia) mutations.
    Time Frame 1 week prior to enrollment

    Outcome Measure Data

    Analysis Population Description
    This data were not and will never be collected
    Arm/Group Title Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 150 mg/m^2 every 12 hours.
    Measure Participants 0
    18. Secondary Outcome
    Title Plasma Inhibitory Activity (PIA)
    Description Analyze the plasma inhibitory activity (PIA) for FLT3 phosphorylation in peripheral blood samples obtained at the time of PK studies in patients with FLT3-ITD mutation AML (Part C).
    Time Frame 1 week prior to enrollment and then every 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 150 mg/m^2 every 12 hours.
    Measure Participants 5
    Count of Participants [Participants]
    5
    71.4%

    Adverse Events

    Time Frame Up to 2 years
    Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
    Arm/Group Title Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Arm/Group Description Patients receive oral sorafenib 105 mg/m^2 every 12 hours Patients receive oral sorafenib 130 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 250 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours. Patients receive oral sorafenib 150 mg/m^2 every 12 hours. Patients receive oral sorafenib 200 mg/m^2 every 12 hours.
    All Cause Mortality
    Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 5/5 (100%) 12/12 (100%) 8/8 (100%) 2/4 (50%) 9/9 (100%) 2/2 (100%) 5/5 (100%) 18/18 (100%)
    Serious Adverse Events
    Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 5/5 (100%) 12/12 (100%) 8/8 (100%) 2/4 (50%) 9/9 (100%) 2/2 (100%) 5/5 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anemia 1/7 (14.3%) 1/5 (20%) 3/12 (25%) 0/8 (0%) 1/4 (25%) 6/9 (66.7%) 2/2 (100%) 4/5 (80%) 0/18 (0%)
    Febrile neutropenia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 7/9 (77.8%) 2/2 (100%) 2/5 (40%) 0/18 (0%)
    Cardiac disorders
    Supraventricular tachycardia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Abdominal pain 0/7 (0%) 0/5 (0%) 3/12 (25%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 2/18 (11.1%)
    Constipation 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Diarrhea 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Dyspepsia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Gastric hemorrhage 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Gastrointestinal disorders - Other, specify 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Intra-abdominal hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Lower gastrointestinal hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Mucositis oral 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Nausea 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Oral hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Oral pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Rectal pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Typhlitis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Vomiting 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    General disorders
    Death NOS 0/7 (0%) 0/5 (0%) 3/12 (25%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Edema face 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Fatigue 0/7 (0%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Non-cardiac chest pain 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Pain 0/7 (0%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 2/5 (40%) 2/18 (11.1%)
    Sudden death NOS 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Immune system disorders
    Anaphylaxis 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Infections and infestations
    Enterocolitis infectious 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Infections and infestations - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 4/9 (44.4%) 2/2 (100%) 2/5 (40%) 0/18 (0%)
    Kidney infection 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Soft tissue infection 0/7 (0%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Alanine aminotransferase increased 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Alkaline phosphatase increased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Aspartate aminotransferase increased 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Blood bilirubin increased 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Creatinine increased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Fibrinogen decreased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    GGT increased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    INR increased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Lipase increased 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Lymphocyte count decreased 2/7 (28.6%) 0/5 (0%) 2/12 (16.7%) 2/8 (25%) 1/4 (25%) 3/9 (33.3%) 2/2 (100%) 5/5 (100%) 2/18 (11.1%)
    Neutrophil count decreased 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 2/8 (25%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 4/5 (80%) 5/18 (27.8%)
    Platelet count decreased 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 0/8 (0%) 0/4 (0%) 8/9 (88.9%) 1/2 (50%) 3/5 (60%) 1/18 (5.6%)
    White blood cell decreased 2/7 (28.6%) 0/5 (0%) 1/12 (8.3%) 2/8 (25%) 0/4 (0%) 3/9 (33.3%) 1/2 (50%) 5/5 (100%) 3/18 (16.7%)
    Metabolism and nutrition disorders
    Acidosis 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Anorexia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 1/5 (20%) 1/18 (5.6%)
    Hyperglycemia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 1/5 (20%) 0/18 (0%)
    Hyperkalemia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypoalbuminemia 0/7 (0%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypocalcemia 0/7 (0%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypoglycemia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Hypokalemia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 3/9 (33.3%) 1/2 (50%) 0/5 (0%) 1/18 (5.6%)
    Hypomagnesemia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Hyponatremia 0/7 (0%) 2/5 (40%) 2/12 (16.7%) 0/8 (0%) 1/4 (25%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypophosphatemia 0/7 (0%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 2/2 (100%) 0/5 (0%) 1/18 (5.6%)
    Tumor lysis syndrome 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Back pain 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 2/5 (40%) 0/18 (0%)
    Pain in extremity 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 0/5 (0%) 2/18 (11.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Nervous system disorders
    Depressed level of consciousness 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Headache 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Peripheral sensory neuropathy 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hematuria 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Epistaxis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypoxia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Pharyngolaryngeal pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Pleural effusion 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Pleuritic pain 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Skin and subcutaneous tissue disorders
    Pain of skin 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Palmar-plantar erythrodysesthesia syndrome 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 2/18 (11.1%)
    Rash maculo-papular 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 3/18 (16.7%)
    Urticaria 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Vascular disorders
    Hypertension 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 2/18 (11.1%)
    Other (Not Including Serious) Adverse Events
    Part A: Refractory Solid Tumors: BAY 43-9006 105 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 130 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 150 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 200 mg/m^2 Part A: Refractory Solid Tumors: BAY 43-9006 250 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 150 mg/m^2 Part B: Refractory Leukemia: BAY 43-9006 200 mg/m^2 Part C: Refractory AML With FLT3-ITD Mutation:150 mg/m^2 PK Cohort Expanded: BAY 43-9006 200 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 5/5 (100%) 12/12 (100%) 8/8 (100%) 2/4 (50%) 9/9 (100%) 2/2 (100%) 5/5 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anemia 3/7 (42.9%) 1/5 (20%) 5/12 (41.7%) 2/8 (25%) 1/4 (25%) 5/9 (55.6%) 1/2 (50%) 3/5 (60%) 7/18 (38.9%)
    Blood and lymphatic system disorders - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 2/18 (11.1%)
    Bone marrow hypocellular 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Lymph node pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Cardiac disorders
    Cardiac disorders - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Paroxysmal atrial tachycardia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Pericardial effusion 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Sinus bradycardia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Sinus tachycardia 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 5/9 (55.6%) 0/2 (0%) 2/5 (40%) 0/18 (0%)
    Ear and labyrinth disorders
    Ear pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    External ear inflammation 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hearing impaired 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Eye disorders
    Blurred vision 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 1/5 (20%) 0/18 (0%)
    Eye pain 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Flashing lights 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Vitreous hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Abdominal pain 3/7 (42.9%) 1/5 (20%) 3/12 (25%) 1/8 (12.5%) 1/4 (25%) 4/9 (44.4%) 1/2 (50%) 2/5 (40%) 3/18 (16.7%)
    Anal mucositis 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Anal pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Cheilitis 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Colitis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Constipation 5/7 (71.4%) 0/5 (0%) 2/12 (16.7%) 1/8 (12.5%) 0/4 (0%) 6/9 (66.7%) 0/2 (0%) 1/5 (20%) 5/18 (27.8%)
    Diarrhea 3/7 (42.9%) 2/5 (40%) 6/12 (50%) 5/8 (62.5%) 2/4 (50%) 6/9 (66.7%) 0/2 (0%) 0/5 (0%) 10/18 (55.6%)
    Dry mouth 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 1/18 (5.6%)
    Dyspepsia 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Dysphagia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Flatulence 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Gastrointestinal disorders - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Lip pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Mucositis oral 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 1/4 (25%) 4/9 (44.4%) 1/2 (50%) 3/5 (60%) 4/18 (22.2%)
    Nausea 3/7 (42.9%) 3/5 (60%) 5/12 (41.7%) 4/8 (50%) 1/4 (25%) 6/9 (66.7%) 1/2 (50%) 3/5 (60%) 6/18 (33.3%)
    Oral hemorrhage 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 3/9 (33.3%) 2/2 (100%) 0/5 (0%) 0/18 (0%)
    Oral pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Periodontal disease 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Proctitis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Rectal hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Rectal pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Stomach pain 1/7 (14.3%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Vomiting 3/7 (42.9%) 1/5 (20%) 5/12 (41.7%) 3/8 (37.5%) 1/4 (25%) 6/9 (66.7%) 1/2 (50%) 4/5 (80%) 7/18 (38.9%)
    General disorders
    Chills 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 2/2 (100%) 1/5 (20%) 0/18 (0%)
    Edema face 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 1/5 (20%) 0/18 (0%)
    Edema limbs 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Fatigue 4/7 (57.1%) 2/5 (40%) 6/12 (50%) 4/8 (50%) 2/4 (50%) 8/9 (88.9%) 1/2 (50%) 5/5 (100%) 11/18 (61.1%)
    Fever 2/7 (28.6%) 0/5 (0%) 4/12 (33.3%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 2/5 (40%) 5/18 (27.8%)
    Flu like symptoms 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Gait disturbance 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Hypothermia 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Non-cardiac chest pain 2/7 (28.6%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Pain 1/7 (14.3%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 3/5 (60%) 5/18 (27.8%)
    Immune system disorders
    Allergic reaction 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 3/9 (33.3%) 1/2 (50%) 1/5 (20%) 1/18 (5.6%)
    Infections and infestations
    Anorectal infection 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Enterocolitis infectious 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Infections and infestations - Other, specify 2/7 (28.6%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 1/4 (25%) 3/9 (33.3%) 1/2 (50%) 2/5 (40%) 0/18 (0%)
    Lung infection 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Otitis media 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Skin infection 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Upper respiratory infection 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 1/18 (5.6%)
    Urinary tract infection 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Injury, poisoning and procedural complications
    Bruising 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 2/8 (25%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 1/5 (20%) 1/18 (5.6%)
    Burn 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Vascular access complication 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 1/7 (14.3%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 5/9 (55.6%) 2/2 (100%) 2/5 (40%) 2/18 (11.1%)
    Alanine aminotransferase increased 1/7 (14.3%) 0/5 (0%) 5/12 (41.7%) 2/8 (25%) 2/4 (50%) 4/9 (44.4%) 2/2 (100%) 4/5 (80%) 10/18 (55.6%)
    Alkaline phosphatase increased 2/7 (28.6%) 0/5 (0%) 3/12 (25%) 0/8 (0%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Aspartate aminotransferase increased 1/7 (14.3%) 1/5 (20%) 8/12 (66.7%) 2/8 (25%) 1/4 (25%) 6/9 (66.7%) 2/2 (100%) 4/5 (80%) 10/18 (55.6%)
    Blood bilirubin increased 2/7 (28.6%) 0/5 (0%) 1/12 (8.3%) 2/8 (25%) 1/4 (25%) 3/9 (33.3%) 1/2 (50%) 1/5 (20%) 6/18 (33.3%)
    Cholesterol high 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Creatinine increased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 0/5 (0%) 3/18 (16.7%)
    Electrocardiogram QT corrected interval prolonged 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Fibrinogen decreased 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    GGT increased 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    INR increased 1/7 (14.3%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 1/5 (20%) 1/18 (5.6%)
    Investigations - Other, specify 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 2/8 (25%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 2/18 (11.1%)
    Lipase increased 2/7 (28.6%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 3/18 (16.7%)
    Lymphocyte count decreased 2/7 (28.6%) 0/5 (0%) 3/12 (25%) 2/8 (25%) 1/4 (25%) 5/9 (55.6%) 0/2 (0%) 1/5 (20%) 9/18 (50%)
    Neutrophil count decreased 2/7 (28.6%) 1/5 (20%) 3/12 (25%) 3/8 (37.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 8/18 (44.4%)
    Platelet count decreased 4/7 (57.1%) 0/5 (0%) 3/12 (25%) 3/8 (37.5%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 3/5 (60%) 11/18 (61.1%)
    Serum amylase increased 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 4/18 (22.2%)
    Weight gain 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Weight loss 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 3/8 (37.5%) 1/4 (25%) 4/9 (44.4%) 0/2 (0%) 1/5 (20%) 3/18 (16.7%)
    White blood cell decreased 4/7 (57.1%) 1/5 (20%) 6/12 (50%) 3/8 (37.5%) 1/4 (25%) 2/9 (22.2%) 1/2 (50%) 2/5 (40%) 6/18 (33.3%)
    Metabolism and nutrition disorders
    Acidosis 0/7 (0%) 2/5 (40%) 3/12 (25%) 0/8 (0%) 1/4 (25%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 2/18 (11.1%)
    Alkalosis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Anorexia 1/7 (14.3%) 2/5 (40%) 1/12 (8.3%) 2/8 (25%) 2/4 (50%) 4/9 (44.4%) 1/2 (50%) 2/5 (40%) 8/18 (44.4%)
    Dehydration 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 1/5 (20%) 0/18 (0%)
    Hypercalcemia 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Hyperglycemia 3/7 (42.9%) 3/5 (60%) 5/12 (41.7%) 2/8 (25%) 1/4 (25%) 8/9 (88.9%) 2/2 (100%) 3/5 (60%) 9/18 (50%)
    Hyperkalemia 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 1/5 (20%) 2/18 (11.1%)
    Hypermagnesemia 3/7 (42.9%) 1/5 (20%) 1/12 (8.3%) 2/8 (25%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 1/5 (20%) 2/18 (11.1%)
    Hypernatremia 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 1/2 (50%) 0/5 (0%) 1/18 (5.6%)
    Hypertriglyceridemia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 1/5 (20%) 1/18 (5.6%)
    Hyperuricemia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Hypoalbuminemia 1/7 (14.3%) 0/5 (0%) 6/12 (50%) 2/8 (25%) 2/4 (50%) 6/9 (66.7%) 2/2 (100%) 4/5 (80%) 2/18 (11.1%)
    Hypocalcemia 2/7 (28.6%) 0/5 (0%) 6/12 (50%) 2/8 (25%) 2/4 (50%) 5/9 (55.6%) 2/2 (100%) 4/5 (80%) 4/18 (22.2%)
    Hypoglycemia 1/7 (14.3%) 1/5 (20%) 1/12 (8.3%) 0/8 (0%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 3/18 (16.7%)
    Hypokalemia 3/7 (42.9%) 1/5 (20%) 7/12 (58.3%) 1/8 (12.5%) 1/4 (25%) 5/9 (55.6%) 2/2 (100%) 2/5 (40%) 8/18 (44.4%)
    Hypomagnesemia 0/7 (0%) 1/5 (20%) 3/12 (25%) 1/8 (12.5%) 2/4 (50%) 4/9 (44.4%) 2/2 (100%) 2/5 (40%) 1/18 (5.6%)
    Hyponatremia 1/7 (14.3%) 0/5 (0%) 4/12 (33.3%) 2/8 (25%) 1/4 (25%) 5/9 (55.6%) 2/2 (100%) 2/5 (40%) 6/18 (33.3%)
    Hypophosphatemia 3/7 (42.9%) 1/5 (20%) 5/12 (41.7%) 2/8 (25%) 2/4 (50%) 5/9 (55.6%) 1/2 (50%) 1/5 (20%) 10/18 (55.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/7 (28.6%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 2/9 (22.2%) 0/2 (0%) 1/5 (20%) 6/18 (33.3%)
    Arthritis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Back pain 2/7 (28.6%) 1/5 (20%) 2/12 (16.7%) 2/8 (25%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 1/5 (20%) 3/18 (16.7%)
    Bone pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Chest wall pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Generalized muscle weakness 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 2/2 (100%) 1/5 (20%) 0/18 (0%)
    Musculoskeletal and connective tissue disorder - Other, specify 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 1/18 (5.6%)
    Myalgia 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 1/8 (12.5%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Neck pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 1/5 (20%) 1/18 (5.6%)
    Osteoporosis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Pain in extremity 3/7 (42.9%) 0/5 (0%) 4/12 (33.3%) 2/8 (25%) 1/4 (25%) 3/9 (33.3%) 0/2 (0%) 1/5 (20%) 3/18 (16.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Nervous system disorders
    Cerebrospinal fluid leakage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Dizziness 1/7 (14.3%) 1/5 (20%) 0/12 (0%) 2/8 (25%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 3/5 (60%) 4/18 (22.2%)
    Dysgeusia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Extrapyramidal disorder 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Facial nerve disorder 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Headache 4/7 (57.1%) 1/5 (20%) 3/12 (25%) 2/8 (25%) 0/4 (0%) 4/9 (44.4%) 2/2 (100%) 3/5 (60%) 2/18 (11.1%)
    Intracranial hemorrhage 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 1/18 (5.6%)
    Memory impairment 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Neuralgia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Peripheral motor neuropathy 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Peripheral sensory neuropathy 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 1/5 (20%) 3/18 (16.7%)
    Sinus pain 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Tremor 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Psychiatric disorders
    Agitation 2/7 (28.6%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Anxiety 1/7 (14.3%) 1/5 (20%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 2/5 (40%) 0/18 (0%)
    Confusion 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 1/5 (20%) 0/18 (0%)
    Depression 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 2/5 (40%) 1/18 (5.6%)
    Hallucinations 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Insomnia 1/7 (14.3%) 1/5 (20%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 3/5 (60%) 2/18 (11.1%)
    Renal and urinary disorders
    Chronic kidney disease 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hematuria 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 3/9 (33.3%) 1/2 (50%) 0/5 (0%) 1/18 (5.6%)
    Proteinuria 3/7 (42.9%) 0/5 (0%) 3/12 (25%) 1/8 (12.5%) 0/4 (0%) 3/9 (33.3%) 1/2 (50%) 1/5 (20%) 3/18 (16.7%)
    Renal and urinary disorders - Other, specify 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Urinary frequency 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Urinary incontinence 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Urinary retention 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 1/4 (25%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Urinary tract pain 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Reproductive system and breast disorders
    Vaginal hemorrhage 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 2/8 (25%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Atelectasis 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Bronchospasm 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Cough 2/7 (28.6%) 0/5 (0%) 0/12 (0%) 2/8 (25%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 4/5 (80%) 4/18 (22.2%)
    Dyspnea 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 3/5 (60%) 2/18 (11.1%)
    Epistaxis 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Hypoxia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 2/5 (40%) 0/18 (0%)
    Pharyngolaryngeal pain 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Pleural effusion 0/7 (0%) 0/5 (0%) 1/12 (8.3%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Pneumonitis 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 1/2 (50%) 0/5 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 2/18 (11.1%)
    Sore throat 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 4/5 (80%) 3/18 (16.7%)
    Dry skin 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 3/8 (37.5%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 3/5 (60%) 3/18 (16.7%)
    Nail loss 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Pain of skin 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Palmar-plantar erythrodysesthesia syndrome 1/7 (14.3%) 1/5 (20%) 2/12 (16.7%) 2/8 (25%) 1/4 (25%) 1/9 (11.1%) 1/2 (50%) 3/5 (60%) 2/18 (11.1%)
    Photosensitivity 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Pruritus 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 3/5 (60%) 2/18 (11.1%)
    Purpura 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 3/9 (33.3%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Rash acneiform 0/7 (0%) 0/5 (0%) 2/12 (16.7%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 1/18 (5.6%)
    Rash maculo-papular 5/7 (71.4%) 1/5 (20%) 5/12 (41.7%) 5/8 (62.5%) 1/4 (25%) 5/9 (55.6%) 0/2 (0%) 4/5 (80%) 8/18 (44.4%)
    Skin and subcutaneous tissue disorders - Other, specify 2/7 (28.6%) 0/5 (0%) 2/12 (16.7%) 0/8 (0%) 1/4 (25%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 1/18 (5.6%)
    Skin hyperpigmentation 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Skin hypopigmentation 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 1/5 (20%) 0/18 (0%)
    Skin ulceration 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 1/18 (5.6%)
    Telangiectasia 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Urticaria 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Vascular disorders
    Flushing 0/7 (0%) 1/5 (20%) 1/12 (8.3%) 1/8 (12.5%) 0/4 (0%) 2/9 (22.2%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hot flashes 0/7 (0%) 0/5 (0%) 0/12 (0%) 1/8 (12.5%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Hypertension 1/7 (14.3%) 0/5 (0%) 1/12 (8.3%) 3/8 (37.5%) 2/4 (50%) 5/9 (55.6%) 1/2 (50%) 2/5 (40%) 4/18 (22.2%)
    Hypotension 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 1/9 (11.1%) 2/2 (100%) 2/5 (40%) 0/18 (0%)
    Thromboembolic event 1/7 (14.3%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 0/2 (0%) 0/5 (0%) 0/18 (0%)
    Vascular disorders - Other, specify 0/7 (0%) 0/5 (0%) 0/12 (0%) 0/8 (0%) 0/4 (0%) 0/9 (0%) 1/2 (50%) 0/5 (0%) 0/18 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 626-447-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01445080
    Other Study ID Numbers:
    • NCI-2009-00358
    • NCI-2009-00358
    • 06-C-0233
    • CDR0000483040
    • COG-ADVL0413
    • NCI-06-C-0233
    • 060233
    • ADVL0413
    • ADVL0413
    • ADVL0413
    • U01CA097452
    • NCT00343694
    • NCT01648413
    First Posted:
    Oct 3, 2011
    Last Update Posted:
    Feb 2, 2021
    Last Verified:
    Jan 1, 2021