NCT01445080 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2021-02-02

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level

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outcome · POSTED

Number of Patients With Treatment-related Adverse Events

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outcome · POSTED

Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib

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outcome · POSTED

Clearance (Cl) of Sorafenib

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outcome · POSTED

Half-life of Sorafenib

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outcome · POSTED

Maximum Serum Concentration (Cmax) of Sorafenib

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outcome · POSTED

Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level

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outcome · POSTED

Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib

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outcome · POSTED

Clearance (Cl) of Sorafenib

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outcome · POSTED

Half-life of Sorafenib

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outcome · POSTED

Volume of Distribution at Steady State (Vss) of Sorafenib

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outcome · POSTED

Maximum Serum Concentration (Cmax) of Sorafenib

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outcome · POSTED

Number of Patients Who Respond Using RECIST Criteria

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outcome · POSTED

Mean Concentration of VEGF2

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outcome · POSTED

Pharmacodynamics (PD) Blood Flow Part C

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outcome · POSTED

Number of Patients With DEMRI

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outcome · POSTED

Leukemia Mutations

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outcome · POSTED

Plasma Inhibitory Activity (PIA)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
maximum Age: 21 Years
minimum Age: 2 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Sorafenib Tosylate
label
Treatment (sorafenib tosylate)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (sorafenib tosylate)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Treatment (sorafenib tosylate)
description
Correlative studies
name
Pharmacological Study
type
OTHER
arm Group Labels
Treatment (sorafenib tosylate)
description
Given orally
name
Sorafenib Tosylate
other Names
BAY 43-9006 Tosylate
BAY 54-9085
Nexavar
sorafenib
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 70
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number of patients with treatment-related dose limiting toxicities in cycle 1, as defined by study protocol, stratified by dose level.
measure
Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level
time Frame
Up to 28 days
description
Number of patients with treatment-related adverse events stratified by dose level through study completion.
measure
Number of Patients With Treatment-related Adverse Events
time Frame
Up to 2 years
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.
measure
Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
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
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.
measure
Clearance (Cl) of Sorafenib
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
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.
measure
Half-life of Sorafenib
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
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.
measure
Maximum Serum Concentration (Cmax) of Sorafenib
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
description
Number of patients with treatment-related dose limiting toxicities in later cycles, as defined by study protocol, stratified by dose level.
measure
Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level
time Frame
Up to 2 years
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.
measure
Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib
time Frame
8 hours post dose on day 1 of cycle 1
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.
measure
Clearance (Cl) of Sorafenib
time Frame
8 hours post dose on day 1 of cycle 1
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.
measure
Half-life of Sorafenib
time Frame
8 hours post dose on day 1 of cycle 1
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.
measure
Volume of Distribution at Steady State (Vss) of Sorafenib
time Frame
8 hours post dose on day 1 of cycle 1
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.
measure
Maximum Serum Concentration (Cmax) of Sorafenib
time Frame
8 hours post dose on day 1 of cycle 1

secondary Outcomes

description
Frequency (%) of patients with Partial Response (PR) or Complete Response (CR) using the RECIST criteria by study part and dose level
measure
Number of Patients Who Respond Using RECIST Criteria
time Frame
Up to 2 years
description
Mean concentration of VEGF2 in peripheral blood sample.
measure
Mean Concentration of VEGF2
time Frame
28 days
description
Pharmacodynamics: tumor blood flow in patients with AML and FLT3-ITD mutation using dynamic contrast enhanced MRI (DEMRI) (Part C).
measure
Pharmacodynamics (PD) Blood Flow Part C
time Frame
1 week prior to enrollment, then every 28 days
description
Assess effect on tumor blood flow via DEMRI in patients with measurable soft tissue tumors.
measure
Number of Patients With DEMRI
time Frame
Up to 2 years
description
Analyze tumor samples and leukemic blasts from patients entered on this study for the presence of ras, raf, or FLT3 (leukemia) mutations.
measure
Leukemia Mutations
time Frame
1 week prior to enrollment
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).
measure
Plasma Inhibitory Activity (PIA)
time Frame
1 week prior to enrollment and then every 28 days

Full 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.
detailed Description: PRIMARY OBJECTIVES: I. Determine the maximum-tolerated dose (MTD) and recommended phase II dose of sorafenib in pediatric patients with relapsed or refractory solid tumors. II. Determine whether pediatric patients with relapsed or refractory leukemia can tolerate the MTD of sorafenib for solid tumors. III. 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. IV. Determine the toxicities of this drug in these patients. V. Determine the pharmacokinetics of this drug in these patients. SECONDARY OBJECTIVES: I. Determine, preliminarily, the antitumor activity of this drug within the confines of a phase I trial. II. Assess the biologic effect of sorafenib on circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF, and VEGF-2 in peripheral blood. III. Assess the gene expression, proteomic profile, and ERK phosphorylation in blasts of patients with refractory leukemia treated with this regimen. IV. 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. V. Analyze tumor samples and leukemic blasts for the presence of ras, raf, or FLT3 (leukemias) mutations. VI. Analyze the plasma inhibitory activity for FLT3 phosphorylation in peripheral blood of patients with AML and FLT3-ITD mutation. VII. 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. VIII. 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.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice