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VEGF Receptor Tyrosine Kinase Inhibitor Axitinib in Children With Recurrent or Refractory Solid Tumors

Phase 1
Completed
Conditions
Refractory or Recurrent Solid Tumors, Excluding CNS Tumors
Interventions
Registration Number
NCT02164838
Lead Sponsor
Children's Oncology Group
Brief Summary

This trial will be the first study of axitinib in children and adolescents. The primary objective of this Phase 1 trial is to determine a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of axitinib in pediatric patients with refractory solid tumors. Additional objectives include measurement of pharmacokinetic and pharmacodynamic parameters, description of the toxicity profile of this agent in children and adolescents, and assessment of response within the confines of a Phase 1 trial. A standard rolling 6 design will be used for dose escalation. Further development of axitinib will focus on development of a joint cooperative group (COG/ECOG) Phase 2 study of axitinib in pediatric, adolescent and young adult translocation renal cell carcinoma.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
51
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AxitinibAxitinib-
Primary Outcome Measures
NameTimeMethod
MTD of axitinib based on dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by CTCAE version 4.028 days
Pharmacokinetic Assessment of Axitinib Concentrations in Plasma SamplesDay 1 and Day 8 of Cycle 1

A descriptive analysis of pharmacokinetic (PK) parameters of axitinib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters.

Blood samples will be collected at the following time points:Day 1, Cycle 1: Pre-dose, and at 1, 2, 4, 6, and 8 hours after the AM dose on Day 1. Day 8, Cycle 1: Pre-dose, and at 1, 2, 4, 6, and 8 hours after the AM dose on Day 8.

Adverse events as assessed by (CTCAE) version 4.028 days
Secondary Outcome Measures
NameTimeMethod
Evaluation of disease response to preliminarily define the antitumor activity of axitinibup to 2 years

Patients will have tumor disease evaluations performed at the end of cycles 1, 3, and 5 and then every 3 cycles. Disease response will be assessed according to RECIST criteria for patients with solid tumors and will be reported descriptively. Analyses will be descriptive and exploratory and hypotheses generating in nature.

Biomarkers of kidney injury during axitinib treatmentCycles 1 and 3

Proteins in the blood (cystatin C and neutrophil gelatinase-associated lipocalcin (NGAL)) and urine (kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), creatinine and other markers of renal injury) will be measured before treatment and then weekly during Cycle 1 of axitinib treatment and at the end of Cycle 3

Trial Locations

Locations (21)

Childrens Hospital of Orange County

🇺🇸

Orange, California, United States

Children's Healthcare of Atlanta - Egleston

🇺🇸

Atlanta, Georgia, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

UCSF Medical Center-Parnassus

🇺🇸

San Francisco, California, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Childrens Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Children's Hospital of Alabama

🇺🇸

Birmingham, Alabama, United States

Ann and Robert H Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Mark O Hatfield-Warren Grant Magnusun Clinical Center

🇺🇸

Bethesda, Maryland, United States

Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

University of Minnesota Cancer Center-Fairview

🇺🇸

Minneapolis, Minnesota, United States

C S Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Midwest Children's Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

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