Phase 2 Completed N=70 Treatment

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

Blastic Phase · leukemia · Childhood Solid Neoplasm · Recurrent Disease

Source: ClinicalTrials.gov NCT01445080 ↗

Enrolled (actual)

Serious AEs

97.1%

Results posted

Feb 2021

Primary outcomePrimary: Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level — 0; 0; 5; 1 Participants

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Patients With Treatment-related Dose Limiting Toxicity in Cycle 1 by Dose Level	0; 0; 5; 1; 2; 0	—
PRIMARY Number of Patients With Treatment-related Adverse Events	6; 3; 12; 7; 2; 6	—
PRIMARY Area Under the Plasma Concentration Versus Time Curve (AUC) of Sorafenib	—	—
PRIMARY Clearance (Cl) of Sorafenib	—	—
PRIMARY Half-life of Sorafenib	—	—
PRIMARY Maximum Serum Concentration (Cmax) of Sorafenib	—	—
PRIMARY Number of Patients With Treatment-related Dose Limiting Toxicities in Later Cycles by Dose Level	0; 0; 1; 1; 1; 1	—
PRIMARY Volume of Distribution at Steady State (Vss) of Sorafenib	—	—
SECONDARY Number of Patients Who Respond Using RECIST Criteria	0; 0; 0; 0; 0; 1	—
SECONDARY Mean Concentration of VEGF2	2650; 247.5; 3531.5; 430; 100	—
SECONDARY Pharmacodynamics (PD) Blood Flow Part C	—	—
SECONDARY Number of Patients With DEMRI	0; 0; 0; 1; 0; 0	—
SECONDARY Leukemia Mutations	—	—
SECONDARY Plasma Inhibitory Activity (PIA)	5	—

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 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 a

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Data sourced from ClinicalTrials.gov (NCT01445080). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.