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Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Endocrine Neoplasia, Recurrent Thyroid Cancer, Thyroid Gland Medullary Carcinoma

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Trial Information

Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma


PRIMARY OBJECTIVES:

I. 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.

II. Determine objective response rate in patients with sporadic metastatic medullary thyroid
carcinoma treated with sorafenib tosylate.

SECONDARY OBJECTIVES:

I. 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.

II. 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.

III. 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.

IV. Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs)
if clinical responses are observed in these patients.

V. Correlate the degree of Ras-MAPK signaling inhibition with vascular endothelial growth
factor (VEGF) expression in the tumor and clinical response in these patients.

VI. 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.

.


Inclusion Criteria:



- 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

- 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

- 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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate of sorafenib tosylate in metastatic medullary thyroid carcinoma in setting of inherited tumor syndromes as well as in setting of sporadic medullary thyroid cancer

Outcome Description:

Measured using MRI scans. Determined using RECIST/WHO response criteria. 95% confidence interval will be calculated to estimate the frequency of response.

Outcome Time Frame:

Every 12 weeks

Safety Issue:

No

Principal Investigator

Manisha Shah

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00196

NCT ID:

NCT00390325

Start Date:

October 2006

Completion Date:

Related Keywords:

  • Multiple Endocrine Neoplasia
  • Recurrent Thyroid Cancer
  • Thyroid Gland Medullary Carcinoma
  • Neoplasms
  • Carcinoma
  • Thyroid Neoplasms
  • Endocrine Gland Neoplasms
  • Multiple Endocrine Neoplasia
  • Thyroid Diseases
  • Carcinoma, Medullary

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210