This phase I trial studies the side effects and best dose of selinexor in treating younger patients with solid tumors or central nervous system (CNS) tumors that have come back (recurrent) or do not respond to treatment (refractory). Drugs used in chemotherapy, such as selinexor, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) or the maximum tolerated dose (MTD) of the tablet formulation of selinexor in children with recurrent/refractory solid and CNS tumors. II. To describe the toxicities of selinexor in children with recurrent/refractory solid and CNS tumors. III. To characterize the pharmacokinetics of the tablet formulation of selinexor in children with recurrent/refractory solid and CNS tumors. SECONDARY OBJECTIVES: I. To determine the antitumor effect of selinexor in a preliminary manner in children with recurrent/refractory solid and CNS tumors. II. To determine the pharmacodynamic properties of selinexor in children and adolescents with refractory solid tumors in plasma proteins and whole blood ribonucleic acid (RNA). III. To explore the penetration, pharmacodynamic effects, and biologic effects of selinexor in tumor tissue of patients with recurrent/refractory high-grade gliomas (HGG) requiring resection. IV. To further assess the toxicity and antitumor effects of selinexor in children with recurrent/refractory HGG in expanded cohorts following dose-escalation by measuring rate of objective radiographic response (medical patients) and rate of progression-free survival (PFS) six months from the start of treatment (surgical patients). OUTLINE: This is a dose escalation study. Patients receive selinexor orally (PO) on either a twice weekly (days 1, 3, 8, 10, 15, 17) or once weekly (days 1, 8, 15, and 22) schedule. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
59
Correlative studies
Given PO
Children's Hospital of Alabama
Birmingham, Alabama, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
...and 13 more locations
Number of Dose Limiting Toxicities of Selinexor
The number of toxicity evaluable patients experiencing a dose limiting toxicity at least possibly attributable to selinexor by study part, schema, and dose level.
Time frame: Up to 28 days
Number of Adverse Events of Selinexor
The number of patients experiencing adverse events at least possibly attributable to selinexor by study part, schema, and dose level.
Time frame: Up to 6 years 11 months
Area Under the Drug Concentration Curve of Selinexor
The median (min, max) of the area under the drug concentration curve evaluated at 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose on day 1 for Selinexor by study part, schema, and dose level.
Time frame: Up to 2 days
Antitumor Effect of Selinexor
Number of patients with best response using RECIST 1.1 criteria of partial response (at least a 30% decrease in the sum of the diameters of target lesions) or complete response (disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm).
Time frame: Up to 6 years 11 months
Pharmacodynamics of Selinexor
Median (min,max) ratio of XPO1 mRNA expression after treatment to pre-treatment by study part, schema, and dose
Time frame: Up to 28 days
Pharmacodynamics of Selinexor in High-grade Glioma (HGG) Patients
Median (min,max) ratio of XPO1 mRNA expression after treatment to pre-treatment by study part, schema, and dose
Time frame: Up to 28 days
Radiographic Response of Selinexor in High-grade Glioma (HGG) Patients
Number of HGG patients with radiographic response by study part, schema, and dose level.
Time frame: Up to 6 years 11 months
Progression-free Survival of Selinexor in Surgical High-grade Glioma (HGG) Patients
Number of surgical HGG patients with 6-month progression-free survival using the Response Evaluation Criteria in solid tumors criteria (RECIST v1.1) defining best response of progressive disease including at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and no prior stable disease, partial response, or complete response.
Time frame: Up to 6 months
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