Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer

• 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 (Multiple endocrine neoplasia, type 2A (MEN 2A) or Multiple endocrine neoplasia, type 2B (MEN 2B) medullary thyroid carcinoma (histologically confirmed) that is unresectable, recurrent or metastatic. Participants must have previously had a characteristic germline mutation in the rearranged during transfection (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 Response Evaluation Criteria in Solid Tumors (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 computed tomography (CT) scan. Superficial (easily palpable) lymph nodes will be considered measurable.

Participants must be able to take one of the oral formulations of vandetanib.

Prior therapy: There are no standard chemotherapy regimens known to be effective for medullary thyroid carcinoma (MTC). Therefore, previously untreated participants 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 polyethylene glycol (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 (Common Terminology Criteria for Adverse Events (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: Prothrombin Time (PT) and Partial Thromboplastin Time (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 aspartate aminotransferase (AST) and alanine aminotransferase (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 m^2.

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.

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