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Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00514046
Recruitment Status : Active, not recruiting
First Posted : August 9, 2007
Last Update Posted : May 8, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


  • 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.


  • 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.


-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).


  • 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 or disease Intervention/treatment Phase
Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia Type 2A Multiple Endocrine Neoplasia Type 2B Drug: Vandetanib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma
Actual Study Start Date : July 20, 2007
Actual Primary Completion Date : December 10, 2019
Estimated Study Completion Date : May 31, 2020

Arm Intervention/treatment
Experimental: Arm 1
Vandetanib administered as a once daily dose, continuously (1 cycle = 28 days) at a dose of 150 mg/m2/d.
Drug: Vandetanib
once daily continuously (28 day cycles)

Primary Outcome Measures :
  1. MTD [ Time Frame: after 4 weeks of drug ]

  2. Objective response (CR or PR) [ Time Frame: every odd cycle ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


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.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00514046

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Brigitte C Widemann, M.D. National Cancer Institute (NCI)
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00514046    
Other Study ID Numbers: 070189
First Posted: August 9, 2007    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: April 23, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Multiple Endocrine Neoplasia
Medullary Thyroid Carcinoma
Molecularly-Targeted Therapy
Additional relevant MeSH terms:
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Thyroid Neoplasms
Endocrine Gland Neoplasms
Multiple Endocrine Neoplasia
Carcinoma, Neuroendocrine
Multiple Endocrine Neoplasia Type 2a
Multiple Endocrine Neoplasia Type 2b
Thyroid Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine System Diseases
Neoplasms by Site
Head and Neck Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue