Anaplastic Thyroid Cancer, Recurrent Thyroid Cancer
Conditions
Brief summary
This phase II trial is studying how well sorafenib works in treating patients with advanced anaplastic thyroid cancer. 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.
Detailed description
OBJECTIVES: I. Determine whether the objective response rate is ≥ 20% in patients with advanced anaplastic thyroid cancer treated with sorafenib. II. Determine the survival of patients treated with this drug. III. Determine the safety profile of this drug in these patients. IV. Determine the pharmacokinetic predictors of response to this drug in these patients. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for survival.
Interventions
DRUGsorafenib tosylate
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Criteria: * Progressive disease after prior cytotoxic chemotherapy (i.e., chemotherapy alone or combined with radiotherapy) * No symptomatic bulky disease that would impair the airway or impede swallowing (for patients with ECOG performance status 2) * No known brain metastases * Measurable or evaluable disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan * Measurable disease not in a previously irradiated field * Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) are eligible provided disease has been stable for the past 6 months * Performance status: * ECOG 0-2 OR Karnofsky 50-100% * Life expectancy more than 8 weeks * Absolute neutrophil count \>= 1,250/mm3 * Platelet count \>= 100,000/mm3 * No evidence of bleeding diathesis * Bilirubin =\< 1.5 times upper limit of normal (ULN) * PTT =\< 1.5 times ULN * Creatinine =\< 1.5 times ULN * No myocardial infarction within the past 6 months * No New York Heart Association class III or IV cardiac disease * No symptomatic congestive heart failure * No unstable angina pectoris * No uncontrolled hypertension (i.e., systolic blood pressure (BP) \> 150 mm Hg OR diastolic BP \> 100 mm Hg) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow oral medication * No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No other invasive malignancy within the past 5 years except nonmelanoma skin cancer * No other uncontrolled illness * No more than 2 prior systemic cytotoxic chemotherapy regimens (combined modality systemic cytoxic chemotherapy is considered 1 prior cytotoxic regimen) * At least 7 days since prior chemotherapy and recovered * At least 7 days since prior radiotherapy and recovered * No prior sorafenib or other inhibitors of MAP kinase signaling intermediates * No prior cancer treatment that would preclude study participation * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) * No concurrent Hypericum perforatum (St. John's wort) or rifampin * No concurrent therapeutic anticoagulation (concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided requirements for INR and PTT are met) * No other concurrent anticancer therapy * Histologically confirmed anaplastic\* thyroid cancer * Not amenable to definitive curative surgery or radiotherapy \[Note: \*Papillary, follicular, or other histologies that are mixed or identified in a diagnostic tissue sample are allowed provided a high-grade undifferentiated anaplastic component is present \] * No cardiac arrhythmia * AST and ALT =\< 3.5 times ULN * INR \< 2.0
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Response to Treatment Measured by RECIST Criteria | at 6 months after treatment | Response evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The patient's best response depends on the achievement of measurement and confirmation criteria of Complete Response (CR), Stable Disease (SD), Partial Response (PR) or Progressive Disease (PD). Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques (CT, MRI, x-ray) or as \>10 mm with spiral CT scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Was Measured From the Date of Outset of Treatment to the Date of Disease Progression. | 27 months | — |
| Overall Survival Was Measured From the Date of Outset of Treatment to the Date of Death. | 27 months | — |
| Number of Participants That Experienced Adverse Events to Characterize the Safety Profile of BAY 43-9006 | 27 months | The safety and toxicity profile of BAY 43-9006 as measured by toxicity grades of adverse events. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from June 2005 to April 2011 from medical clinics
Participants by arm
| Arm | Count |
|---|---|
| BAY 43-9006 BAY 43-9006 (sorafenib) will be administered on a fixed daily oral dosing schedule of 400 mg twice daily. A cycle of therapy will be considered 28 days (4 weeks / 1 month). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | BAY 43-9006 |
|---|---|
| Age, Continuous | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 8 / 20 |
Outcome results
Primary
Number of Patients With Response to Treatment Measured by RECIST Criteria
Response evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The patient's best response depends on the achievement of measurement and confirmation criteria of Complete Response (CR), Stable Disease (SD), Partial Response (PR) or Progressive Disease (PD). Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques (CT, MRI, x-ray) or as \>10 mm with spiral CT scan.
Time frame: at 6 months after treatment
Population: All patients that received at least one cycle of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAY 43-9006 | Number of Patients With Response to Treatment Measured by RECIST Criteria | Partial Response | 2 participants |
| BAY 43-9006 | Number of Patients With Response to Treatment Measured by RECIST Criteria | Stable Disease | 5 participants |
| BAY 43-9006 | Number of Patients With Response to Treatment Measured by RECIST Criteria | Progressive Disease | 11 participants |
Secondary
Number of Participants That Experienced Adverse Events to Characterize the Safety Profile of BAY 43-9006
The safety and toxicity profile of BAY 43-9006 as measured by toxicity grades of adverse events.
Time frame: 27 months
Population: Any participant that received treatment was analyzed for adverse events. Detailed information is reported in the Adverse Events data table.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BAY 43-9006 | Number of Participants That Experienced Adverse Events to Characterize the Safety Profile of BAY 43-9006 | 20 Participants |
Secondary
Overall Survival Was Measured From the Date of Outset of Treatment to the Date of Death.
Time frame: 27 months
Population: All patients on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAY 43-9006 | Overall Survival Was Measured From the Date of Outset of Treatment to the Date of Death. | 3.9 months |
Secondary
Progression Free Survival Was Measured From the Date of Outset of Treatment to the Date of Disease Progression.
Time frame: 27 months
Population: All patients on study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAY 43-9006 | Progression Free Survival Was Measured From the Date of Outset of Treatment to the Date of Disease Progression. | 1.9 months |