ADV1416: A Study of Ramucirumab in Children with Solid Tumors and Brain Tumors

A Phase I Study of Ramucirumab, a Human Monoclonal Antibody Against the Vascular Endothelial Growth Factor-2 (VEGFR-2) Receptor in Children with Refractory Solid Tumors, Including CNS Tumors

Categories:

Brain Tumor

Solid Tumor

Phase I/II

Diseases Treated:

Brain Tumors

Solid Tumors

Eligibility Overview:

  • 12 months old or older and younger than 21 years old
  • Diagnosis:
    • Part A - Non-central nervous system (CNS) tumor that returned after treatment or did not respond to treatment
    • Part B – CNS tumor that returned after treatment or did not respond to treatment
  • No other proven therapy options
  1. Brief Summary

    This study will seek to determine the safety and antitumor activity of ramucirumab in pediatric patients with recurrent or refractory solid tumors, including central nervous system tumors. Ramucirumab is a highly selective human monoclonal antibody directed against the vascular endothelial growth factor-2 receptor (VEGFR-2). Preclinical studies have demonstrated its effectiveness as a single agent or in combination with doxorubicin in pediatric patient-derived xenograft sarcoma models. It is approved by the U.S. Food and Drug Administration for use in adults with advanced gastro-esophageal cancer and metastatic non-small cell lung cancer but is not approved for use in children.

    Primary Objectives

    • To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ramucirumab administered as an intravenous infusion over 60 minutes, every 2 weeks, to children with recurrent or refractory solid tumors
    • To determine the tolerability of the MTD and/or RP2D of ramucirumab in children with recurrent or refractory CNS tumors
    • To define and describe the toxicities of ramucirumab administered on this schedule
    • To characterize the pharmacokinetics and immunogenicity of ramucirumab in children with recurrent or refractory solid tumors including CNS tumors

    Eligibility Criteria

    Inclusion criteria include:

    • 12 months old or older and younger than 21 years old
    • Diagnosis:
      • Part A - Non-central nervous system (CNS) tumor that returned after treatment or did not respond to treatment. (Exception: patients with extra-cranial germ-cell tumors and elevations of serum tumor markers including alpha-fetoprotein or beta-HCG.)
      • Part B – CNS tumor that returned after treatment or did not respond to treatment. (Exception: patients with intrinsic brain stem tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG.)
    • No known curative therapy or therapy proven to prolong survival with acceptable quality of life
    • Karnofsky performance level ≥50% for participants older than 16 years
    • Lansky performance level ≥50% for participants 16 years old and younger

    Exclusion Criteria include:

    • Pregnancy or breastfeeding
    • Major surgery or certain surgical procedures
    • Chronically receiving aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs
    • Currently receiving:
      • another investigational drug
      • another anti-cancer agent
      • cyclosporine, tacrolimus or other agents used to prevent graft-versus-host disease
      • anti-platelet agents
      • anti-hypertensive medications
      • therapeutic anti-coagulation with heparin, low-molecular weight heparin or Coumadin
      • belimumab, a monoclonal antibody for systemic lupus erythematosus
      • bisphosphonate derivatives
    • Evidence of active bleeding
    • Known cardiac disease
    • HIV or other immunocompromising infection
    • Previous solid organ transplant

    Study Sites

    St. Jude Children’s Research Hospital and collaborating sites in the U.S.
    Memphis, Tennessee

  2. About this study

    This study will test an experimental drug called ramucirumab. Other studies have found that this drug seems to work well against cancer in test tubes and animals. It has also been used in adults but not in children. In this study, ramucirumab will be given to children for the first time. Researchers want to find out if the drug will work against cancer that has come back after treatment or not responded to treatment.

    Purpose of this clinical trial

    The main goal of this study is to find the highest dose of ramucirumab that may be given safely to children.

    Eligibility overview

    • 12 months old or older and younger than 21 years old
    • Diagnosis:
      • Part A - Non-central nervous system (CNS) tumor that returned after treatment or did not respond to treatment
      • Part B – CNS tumor that returned after treatment or did not respond to treatment
    • No other proven therapy options
  3. ADV1416 Quick View
    Sponsors Eli Lilly and Co. with Children’s Oncology Group
    ClinicalTrials.gov identifier NCT02564198
    Trial Start Date December 2015
    Estimated Enrollment 36
    Study Type Interventional
    Study Phase Phase I
    Conditions Solid Tumor
    Ages Between 12 months and 21 years old
    Principal investigator Wayne Furman, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in the U.S.
    For a consultation or to discuss ADV1416 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Wayne Furman, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

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