Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00514046
First received: August 8, 2007
Last updated: May 15, 2014
Last verified: October 2013
  Purpose

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 effects of Vandetanib.
  • Blood tests and imaging scans (MRI, CT, bone and octreoscan) are done every 8 weeks for the first 32 weeks of treatment and then every 16 weeks for the duration of the treatment period.
  • Patients who have tumor-related diarrhea keep a daily record of the number and consistency of bowel movements.

Condition Intervention Phase
Multiple Endocrine Neoplasia Type 2A
Multiple Endocrine Neoplasia Type 2B
Drug: ZACTIMA (Vandetanib)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Objective response (complete or partial) as assessed by RECIST [ Designated as safety issue: No ]
  • Change in tumor markers (calcitronin and CEA) [ Designated as safety issue: No ]
  • Change in tumor-related diarrhea [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Expression of RET, EGFR, VEGFR, and somatostatin receptor by IHC [ Designated as safety issue: No ]
  • Tumor pharmacodynamics [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: July 2007
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ZACTIMA (Vandetanib)
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Age: Participants must be 5 to 18 years of age, inclusive. The first cohort of 3 to 6 participants enrolled on the trial will be at least 13 years of age.

Diagnosis: Hereditary (MEN 2A or MEN 2B) medullary thyroid carcinoma (histologically confirmed) that is unresectable, recurrent or metastatic. Participants must have previously had a characteristic germline mutation in the RET proto-oncogene documented. Results of the germline mutation testing will be obtained from the referring institution.

Participants must have measurable disease as defined in RECIST as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter of at least 20 mm using conventional techniques or at least 10 mm with spiral CT scan. Superficial (easily palpable) lymph nodes will be considered measurable.

Participants must be able to take one of theoral formulations of vandetanib.

Prior therapy: There are no standard chemotherapy regimens known to be effective for MTC. Therefore, previously untreated partipants are eligible if their tumor(s) are not surgically resectable.

Participants must be at least 4 weeks from prior surgical procedures and surgical incisions must be healed.

Participants must have had their last fraction of external beam radiation therapy at least 4 weeks prior to enrollment.

Participants must have had their last dose of cytotoxic chemotherapy at least 28 days prior to enrollment, their last dose of biological therapy, such as biological response modifiers (e.g., cytokines), immunomodulatory agents, vaccines, differentiating agents, used to treat their cancer at least 7 days prior to enrollment, their last dose of a monoclonal antibody at least 30 days prior to enrollment, and their last dose of any investigational agent at least 30 days prior to enrollment.

Participants must have received their last dose of short acting colony stimulating factor, such as filgrastim or sargramostim at least 72 hours prior to enrollment and their last dose of long-acting colony stimulating factors, such as PEG-filgrastim at least 7 days prior to enrollment.

Participants must have recovered from the acute toxic effects of prior therapy to a grade 1 (CTCAE v.3.0) level prior to enrollment.

Performance Status: Lansky (for participants 10 years of age or younger) or Karnofsky (for participants older than 10 years) performance score greater than 50

Concomitant Medications:

Participants who have previously had a thyroidectomy should be on thyroid hormone replacement therapy.

Hematological Function: The peripheral absolute neutrophil count must be at least 1,500 micro liters and the platelet count must be at least 100,000 micro liters within 72 hours prior to enrollment.

Coagulation: PT and PTT must not be more than 1.5 x ULN within 72 hours prior to enrollment. PT and PTT should drawn by venipuncture, rather than from a central venous catheter when feasible.

Hepatic Function:

Bilirubin must not be more than 1.5 x ULN and the AST and ALT must not be more than 2.5 x ULN within 72 hours prior to enrollment. AST and ALT may be up to 5 x ULN within 72 hours prior to enrollment in participants with hepatic metastases.

Renal Function: Participants must have an age-adjusted normal serum creatinine or a creatinine clearance of at least 60 ml/min/1.73 m2.

Birth Control: Participants of child-bearing or child-fathering potential must be willing to use a medically effective form of birth control, which includes abstinence, while taking vandetanib and for 2 months after the last dose.

Negative pregnancy test for women of childbearing potential.

Informed Consent: Participants who are 18 years of age or legal guardians of participants who are younger than 18 years must sign an informed consent for the POB Screening Protocol prior to participating in studies required to determine eligibility for this trial. After confirmation of eligibility, participants or legal guardians of minor participants must sign an informed consent document for this trial, indicating that they are aware of the investigational nature of the proposed treatment, the risks and benefits of participating and the alternatives to participating.

EXCLUSION CRITERIA:

Pregnant or breast feeding females because the anti-angiogenic properties of vandetanib may be harmful to the developing fetus or nursing infant.

Participants with pheochromocytoma as evidenced by elevated plasma free metanephrines.

Electrolytes: Participants with a serum potassium less than 3.5 mmol/L or a serum calcium or magnesium below the lower limits of normal. Correction of these electrolyte abnormalities with supplements is allowed.

Cardiac:

Participants with a history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle branch block) that is symptomatic or requires treatment (except for controlled atrial fibrillation)

Participants with a history of congenitally prolonged QTc, a first degree relative with unexplained sudden death under 40 years of age, or a measured QTc (Bazett s correction) longer than 480 msec on ECG. ECGs should be performed after correction of electrolyte abnormalities. Participants with a prolonged QTc should have a repeat ECG at least 24 hour after the first, and the mean of the 2 QTcs should not exceed 480 msec.

Participants who experienced QTc prolongation with other medications requiring discontinuation of that medication.

Participants receiving a medication that has a known risk of QTc prolongation within 14 days (28 days for levomethadyl) of enrollment.

Hypertension: Diastolic blood pressure above the 95% for age on at least 2 of 3 measurements with an appropriate-size cuff or patients who are currently taking anti-hypertensive therapy.

Other clinically severe or uncontrolled systemic illness that could compromise the participants ability to tolerate vandetanib or could compromise study procedures or endpoints.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00514046

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Brigitte C Widemann, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00514046     History of Changes
Other Study ID Numbers: 070189, 07-C-0189
Study First Received: August 8, 2007
Last Updated: May 15, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Multiple Endocrine Neoplasia (MEN)
Medullary Thyroid Carcinoma
Molecularly-Targeted Therapy
Pediatric
Pharmacokinetics
MTC
Multiple Endocrine Neoplasia
MEN

Additional relevant MeSH terms:
Neoplasms
Thyroid Neoplasms
Endocrine Gland Neoplasms
Multiple Endocrine Neoplasia Type 2a
Multiple Endocrine Neoplasia Type 2b
Multiple Endocrine Neoplasia
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 28, 2014