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

NCT02164838 | Completed Phase 1 DMC

• 1 other identifier: ADVL1315
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 21

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.

Conditions

Refractory or Recurrent Solid Tumors, Excluding CNS Tumors

Outcome Measures

Primary Outcomes (3)

• Adverse events as assessed by (CTCAE) version 4.0

  28 days

• MTD of axitinib based on dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by CTCAE version 4.0

  28 days

• Pharmacokinetic Assessment of Axitinib Concentrations in Plasma Samples

  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.

  Day 1 and Day 8 of Cycle 1

Secondary Outcomes (2)

• Evaluation of disease response to preliminarily define the antitumor activity of axitinib

  up to 2 years

• Biomarkers of kidney injury during axitinib treatment

  Cycles 1 and 3

Study Arms (1)

Axitinib

EXPERIMENTAL

Drug: Axitinib

Interventions

Axitinib DRUG

Also known as: AG-013736, INLYTA®

Axitinib

Eligibility Criteria

• Age: 12 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: Patients must be \> than 12 months and \< 18 years of age at the time of study enrollment.
• Body Surface Area: Patients must have a BSA of ≥ 0.53 m2 at the time of study enrollment.
• Diagnosis: Patients with refractory or recurrent solid tumors (excluding CNS tumors) and patients with unresectable translocation positive renal cell carcinoma (tRCC) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
• The diagnosis of translocation morphology or TFE renal cell carcinoma is established by having characteristic morphology AND either a) strong nuclear TFE3 or TFEb staining on immunohistochemistry OR b) cytogenetic studies of the tumor demonstrating a TFE translocation OR c) fluorescent in situ hybridization (FISH) demonstrating a TFE translocation.
• Disease Status: Patients must have either measurable or evaluable disease
• Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age . Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy
• Patients may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine kinase inhibitors, but may not have received axitinib.
• Patients must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria, hypertension).
• All patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy.
• Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.

You may not qualify if:

• Pregnancy or Breast-Feeding
• Corticosteroids: Patients receiving chronically dosed corticosteroids within 7 days prior to enrollment are not eligible for this trial.
• Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
• Anti-GVHD agents post-transplant:
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• CYP3A4/5 Inhibitors:
• Patients chronically receiving drugs that are known potent CYP3A4/5 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit, and grapefruit juice are not eligible
• CYP3A4/5 Inducers:
• Patients chronically receiving drugs that are known potent CYP3A4/5 inducers within 7 days prior to study enrollment, including but not limited to rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and St John's wort are not eligible.
• Anti-hypertensives: Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial.
• Anti-coagulation: Patients who are currently receiving therapeutic anti-coagulation with heparin, low-molecular weight heparin or coumadin are not eligible for this trial.
• Anti-inflammatory or anti-platelet agents: Patients who are currently receiving aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs or anti-platelet agents are not eligible.
• Patients must be able to swallow tablets whole.
• Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 28 days prior to study enrollment. Patients who enter the study on thyroid replacement should have their medication adjusted to maintain TSH in the normal range.

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (21)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Mark O Hatfield-Warren Grant Magnusun Clinical Center

Bethesda, Maryland, 20892, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48108, United States

Location

University of Minnesota Cancer Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98145, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Interventions

Axitinib

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• James Geller, MD

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2014
• First Posted: June 17, 2014
• Study Start: September 1, 2014
• Primary Completion: October 19, 2017
• Study Completion: October 19, 2017
• Last Updated: January 29, 2018

Record last verified: 2018-01

Locations

CA (1); US (20)