Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer

Official Title: “Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma”

RATIONALE: Sorafenib 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 sorafenib works in treating patients with metastatic, locally advanced, or recurrent medullary thyroid cancer.

OBJECTIVES:

Primary - Determine objective response rate in patients with metastatic, locally advanced, or recurrent medullary thyroid carcinoma in a setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC), treated with sorafenib tosylate. - Determine objective response rate in patients with sporadic metastatic medullary thyroid carcinoma treated with sorafenib tosylate.

Secondary - Determine toxicity of sorafenib in these patients. - Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment and correlate with disease response in these patients. - Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 positron emission tomography [PET] scan) data obtained at pre-, during, and post-treatment with tumor response in these patients. - Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity and tumor response in these patients. - Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed in these patients. - Correlate the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response in these patients. - Correlate the presence and type of RET gene defects in tumor with clinical response in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical setting of disease (inherited tumor syndromes vs sporadic).

Patients receive oral sorafenib tosylate twice daily on days 1-56. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection and tumor biopsies for biomarker/laboratory studies (immunohistochemistry, pharmacogenomic studies, and genotyping) at baseline, every 8 weeks during treatment, and after completion of study treatment. Tumor markers may include carcinoembryonic antigen (CEA), calcitonin, and RET mutations.

After completion of study treatment, patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: sorafenib tosylate
• Genetic: molecular genetic technique
• Genetic: mutation analysis
• Other: immunohistochemistry staining method
• Other: laboratory biomarker analysis
• Other: pharmacological study

Primary Measures

• Objective response rate
  • Safety Issue?: No

Secondary Measures

• Toxicity
  • Safety Issue?: Yes
• Correlation of serum tumor markers calcitonin and carcinoembryonic antigen (CEA) measurements with disease response at baseline, every 8 weeks during treatment, and after completion of treatment
  • Safety Issue?: No
• Correlation of nuclear medicine functional imaging data by fludeoxyglucose F 18 positron emission tomography (PET) scan with tumor response
  • Safety Issue?: No
• Correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data with changes in tumor permeability and vascularity and tumor response
  • Safety Issue?: No
• Pharmacogenomics on procured peripheral blood mononuclear cells (PBMCs) in the setting of clinical response
  • Safety Issue?: No
• Correlation of the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response
  • Safety Issue?: No
• Correlation of the presence and type of RET gene defects in the tumor with clinical response
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed medullary thyroid carcinoma (MTC) meeting 1 of the following criteria:
• Inherited tumor syndromes (e.g., multiple endocrine neoplasia [MEN] 2A, MEN 2B, or familial medullary thyroid carcinoma [FMTC])
• Sporadic MTC
• Metastatic and/or locally advanced or locally recurrent disease
• Measurable disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 6 months
• WBC ≥ 2,000/mm³
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Creatinine normal OR creatinine clearance > 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate
• No condition that impairs ability to swallow pills
• No uncontrolled intercurrent illness, including, but not limited to, any of the following:
• Ongoing or active infection
• Uncontrolled hypertension
• Psychiatric illness or social situation that would preclude study compliance
• No evidence of a bleeding diathesis

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior systemic antitumor therapy (e.g., chemotherapy, biologic modifiers, or antiangiogenic therapy) (6 weeks for nitrosourea or mitomycin C)
• More than 1 week since prior external beam radiotherapy and recovered
• No prior sorafenib, ZD6474, or AMG-706
• No other concurrent tumor-specific therapy for thyroid cancer or investigational therapy
• Concurrent adjuvant hormonal therapy for a second primary (e.g., breast cancer or prostate cancer) allowed if no known drug interactions
• Concurrent oral or IV bisphosphonates allowed for patients with bone metastases
• No concurrent active anticoagulation with therapeutic intent
• Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the PT, INR, or PTT are normal
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Other

Overall Clinical Trial Officials and Contacts

Manisha H. Shah, MD Study Chair Arthur G. James Cancer Hospital & Richard J. Solove Research Institute  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00390325

Study ID Number: CDR0000507441

ClinicalTrials.gov Identifier: NCT00390325

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database