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Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2009
First Received: June 22, 2006   Last Updated: November 3, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00343694
  Purpose

RATIONALE: 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.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib in treating young patients with relapsed or refractory solid tumors or leukemia.


Condition Intervention Phase
Leukemia
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: sorafenib tosylate
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor BAY 43-9006 (Sorafenib, NSC# 724772, IND# 69896) in Children With Refractory Solid Tumors or Refractory Leukemias

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose and recommended phase II dose [ Designated as safety issue: Yes ]
  • Toxic effects [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Preliminary antitumor activity [ Designated as safety issue: No ]

Estimated Enrollment: 63
Study Start Date: May 2006
Estimated Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) and recommended phase II dose of sorafenib in pediatric patients with relapsed or refractory solid tumors.
  • Determine whether pediatric patients with relapsed or refractory leukemia can tolerate the MTD of sorafenib for solid tumors.
  • Determine the toxic effects of this drug in these patients.
  • Determine the pharmacokinetics of this drug in these patients.

Secondary

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

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

  • Stratum 1 (refractory solid tumor patients): Patients receive oral sorafenib twice daily on days 1-28. Some patients undergo pharmacokinetic (PK) sampling in course 1 during which time doses 2 and 3 of study drug are withheld (excluding patients enrolled on the expanded PK cohort and patients with refractory leukemia enrolled at the solid tumor MTD). 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 2 (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.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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)
      • 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

PATIENT CHARACTERISTICS:

  • 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)
  • 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 (sum of conjugated + unconjugated) ≤ upper limit of normal (ULN) for age
    • ALT ≤ ULN for age (for the purpose of this study, the ULN for ALT is 45 μ/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 μ/L) (for the purpose of this study, the ULN for ALT is 45 μ/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
  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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)
  • 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 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
  • 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's 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00343694

  Show 23 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Brigitte C. Widemann, MD NCI - Pediatric Oncology Branch
Investigator: Elizabeth Fox, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000483040, COG-ADVL0413, NCI-06-C-0233
Study First Received: June 22, 2006
Last Updated: November 3, 2009
ClinicalTrials.gov Identifier: NCT00343694     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
childhood acute promyelocytic leukemia (M3)
Philadelphia chromosome negative chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
childhood chronic myelogenous leukemia
juvenile myelomonocytic leukemia

Additional relevant MeSH terms:
Leukemia
Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Sorafenib
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2009