Clinical Trial: Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma

Brief Summary:

Background:

  • Medullary thyroid carcinoma (MTC) is common in people with a genetic disorder called multiple endocrine neoplasia (MEN).
  • Vandetanib is an experimental drug that blocks a defective protein receptor (RET receptor) found on the surface of cancer cells in people with MEN. It is thought that this protein is a primary cause of MTC in people with MEN.

Objectives:

  • To study the activity of Vandetanib in children and adolescents with MEN-related MTC by measuring the change in tumor size, in blood levels of proteins produced the tumor (calcitonin and CEA) and in tumor-related diarrhea.
  • To determine the safety and tolerability of Vandetanib in children and adolescents.
  • To study how the body handles Vandetanib in children and adolescents.
  • To determine the effect of Vandetanib on the survival of children and adolescents with MTC.

Eligibility:

-Children and adolescents 5 to 18 years of age with MTC whose tumor cannot be surgically removed or has grown back after treatment or has metastasized (spread beyond the thyroid gland).

Design:

  • Patients take Vandetanib once a day in 28-day cycles. The first patients enrolled in the study are started on a low dose of Vandetanib to determine tolerability.
  • Patients have periodic blood tests, electrocardiograms, and blood pressure measurements to look for side effec

    Detailed Summary:

    BACKGROUND:

    Hereditary medullary thyroid carcinoma (MTC), which is a rare calcitonin-producing tumor arising from the parafollicular C cells of the thyroid, is often a manifestation of multiple endocrine neoplasia (MEN) types 2A and 2B and can be detected in children as young as five years in MEN 2A and one year in those with MEN 2B

    MEN results from an activating mutation in the RET proto-oncogene resulting in a constitutively activated receptor tyrosine kinase (RTK)

    Vandetanib is an orally bioavailable multi-RTK inhibitor that blocks the mutant RET gene product and has anti-tumor activity in adults with hereditary MTC

    OBJECTIVES:

    To assess the activity of vandetanib in children and adolescents with hereditary MTC using RECIST (primary endpoint), tumor biomarkers and tumor-related diarrhea

    To assess the safety and tolerance of navdetanib in children and adolescents at a dose equivalent to the recommended dose in adults

    To assess the pharmacokinetics of vandetanib at steady state in children and adolescents

    Secondary objectives include monitoring progression-free and overall survival, assessing RET, EGFR, VEGFR andsomatostatin receptor expression in archival tumor tissue, assessing changes in DNA mutations in RET in tumor tissue vs germ line in PBMC and after treatment; assessing gene expression and gains/lossess of DNA in tumor tissue at baseline, during treatment and at the time of progression; establishment of pediatric MTC cell lines sensitive and resistant cells lines in vitro

  • Assess pharmacokinetics of vandetanib at steady state [ Time Frame: pre dose 1, 24 hrs after 1st dose, pre cycle 2, and post cycle 2 (this will include thorough eval) ]
  • Assess safety and tolerance [ Time Frame: after 4 weeks of drug ]
  • Assess the activity of vandetanib in children with MTC [ Time Frame: every odd cycle ]


Original Primary Outcome:

  • Objective response (complete or partial) as assessed by RECIST
  • Safety
  • Maximum tolerated dose
  • Pharmacokinetics


Current Secondary Outcome:

  • Assess a variety of research endpoints including expression of RET, EGFR, VEGFR and somatostatin, assess gene expression and screen for gains or losses of DNA sequences [ Time Frame: at time of biopsy ]
  • Determine progression free survival and overall survival [ Time Frame: after every 2 cycles X4, then after every 4 cycles ]


Original Secondary Outcome:

  • Toxicity
  • Progression-free survival
  • Overall survival
  • Expression of RET, EGFR, VEGFR, and somatostatin receptor by IHC


Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: August 8, 2007
Date Started: July 9, 2007
Date Completion: July 27, 2020
Last Updated: May 12, 2017
Last Verified: September 26, 2016