Everolimus in Treating Patients With Locally Advanced or Metastatic Thyroid Cancer

An Open Label Multi-Center Phase II Study of RAD001 in Advanced Thyroid Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with locally advanced or metastatic thyroid cancer.

OBJECTIVES:

Primary

• To evaluate response rate in patients with locally advanced or metastatic, unresectable or refractory thyroid cancer treated with everolimus.

Secondary

• To evaluate overall survival of these patients treated with everolimus.
• To evaluate progression-free survival of these patients.
• To evaluate toxicity of this therapy in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for correlative studies.

After completion of study treatment, patients are followed up for 12 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed thyroid cancer

  • Progressive or refractory disease within the past 6 months
  • Locally advanced or metastatic disease

• Measurable disease, defined as ≥ 1 measurable lesion defined by RECIST criteria

• Not amenable to surgical resection or external-beam radiotherapy or refractory to radioiodine therapy

• No untreated brain metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Creatinine < 1.5 mg/dL
• Total bilirubin ≤ 1.0 times upper limit of normal (ULN)
• ALT and AST ≤ 3.0 times ULN
• No known hypersensitivity to the study drug
• No serious uncontrolled systemic intercurrent illness (e.g., infection or poorly controlled diabetes)
• No history of significant neurological or mental disorder, including seizures or dementia
• No other malignancy within the past 5 years except for carcinoma in situ of the cervix or nonmelanomatous carcinoma of the skin
• No active uncontrolled cardiac disease
• No myocardial infarction within the past 12 months
• Able to take oral medication
• No active peptic ulcer disease
• Must have patient compliance and geographic proximity for adequate follow-up

PRIOR CONCURRENT THERAPY:

• At least 30 days since prior mTor-inhibitor therapy (e.g., temsirolimus) or non-hormonal anticancer therapy
• At least 2 weeks since prior and no concurrent P-glycoprotein, CYP3A4, and CYP3A5 inhibitors or inducers
• No prior surgical procedure affecting absorption
• No other concurrent systemic chemotherapy, investigational drug, or radiotherapy