Metastatic Anaplastic Thyroid Cancer, Metastatic Differentiated Thyroid Cancer, Metastatic Medullary Thyroid Cancer, Metastatic Poorly Differentiated Thyroid Cancer
Conditions
Keywords
Thyroid Cancer, Anaplastic, Medullary, sorafenib
Brief summary
The goal of this study is to determine the activity of sorafenib in patients with advanced (metastatic or recurrent) thyroid cancer.
Interventions
DRUGsorafenib
400mg PO BID daily
Sponsors
University of Pennsylvania
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
* Patients must have histologically confirmed thyroid cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. * Patients may have received multiple treatments of radioactive iodine, one prior biologic treatment, and at least half of the patients will have had no prior chemotherapy for metastatic disease. At least 3 weeks must have elapsed since prior treatment. * Measurable disease defined as at least one malignant lesion that can be accurately and serially measured in at least one dimension (longest diameter to be recorded), using a caliper (diameter \> 10 mm) for superficial cutaneous disease, or using contrast-enhanced CT or spiral CT (diameter \> 20 mm) for visceral or nodal/soft tissue disease. * ECOG performance status \< 2 (Appendix 1). * Life expectancy greater than 3 months. * Adequate organ function that has been determined within 7 days prior to enrollment, defined as:Leucocyte count \> 3,000/uL; Absolute neutrophil count (ANC) \> 1,500/mm3, platelets \> 100,000/mm3, and hemoglobin \> 9 g/dl; Serum creatinine \< 1.5 times ULN, or 24-hour creatinine clearance \> 75 cc/min. (Note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits); Serum bilirubin \< 1.5 times ULN; serum glutamyloxaloacetic transaminase (SGOT) \< 2.5 ULN; alkaline phosphatase \< 2.5 times ULN; PT-INR/PTT \< 1.5 x upper limit of normal. * Intellectual, emotional, and physical ability to comply with oral medication. * Ability to understand and the willingness to sign a written informed consent * Patients with disease accessible for biopsy will be preferentially selected for participation in the study. Accessible disease includes lymph node metastases. * Female patients of child-bearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-child-bearing potential. Male and female patients of reproductive potential must agree to use adequate contraception (i.e. hormonal or barrier method of birth control). throughout the study and for 3 months after the study.
Exclusion criteria
* Significant medical disease including: uncontrolled congestive heart failure; active symptoms of coronary artery disease, uncontrolled seizure disorder; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment; requirement for concurrent immunosuppressive drug(s); active autoimmune disease. * Organ allografts. * Known HIV-infection (HIV testing is not required for participation). * Pregnancy or lactation. Women of childbearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment * History of second cancer (except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five or more years). * Use of any experimental therapy within 3 weeks prior to baseline evaluations done prior to enrollment. * Patients with carcinomatous meningitis are excluded from the study. * Excluded therapies and medications, previous and concomitant:Anticancer chemotherapy or immunotherapy during the study or within 4 weeks prior to the first dose of the study drug; Radiotherapy for the treatment of a symptomatic (e.g. bone metastasis) as clinically indicated is allowed as long as it is not evidence of progressive disease (see 4.5.2); -Biological response modifiers, such as G-CSF, within 3 week prior to study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction); Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study; Investigational drug therapy outside of this trial during or within 4 weeks prior the screening assessment; Use of ketoconazole, itraconazole, and ritonavir; Use of carbamazepine, phenytoin, phenobarbital; Previous exposure to a Ras pathway inhibitor (including herceptin, EGFr inhibitors, farnesyl transferase inhibitors or MEK inhibitors); Use of grapefruit juice products; Use of cyclosporin; * Pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib). | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | This is the result of the Kaplan Meier analysis of all patients treated with sorafenib |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib This is a single arm study.
sorafenib: 400mg PO BID daily | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen Failures | 4 |
Baseline characteristics
| Characteristic | Sorafenib | — |
|---|---|---|
| Age, Continuous | 63 years | — |
| ECOG Performance Status at Baseline ECOG Performance Status 0 | 29 Participants | — |
| ECOG Performance Status at Baseline ECOG Performance Status 1 | 26 Participants | — |
| Histology subtype Anaplastic | 2 Participants | — |
| Histology subtype DIfferentiated | 44 Participants | — |
| Histology subtype Medullary | 3 Participants | — |
| Histology subtype Poorly Differentiated | 6 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 55 participants | — |
| Sex: Female, Male Female | 27 Participants | — |
| Sex: Female, Male Male | 28 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 36 / 55 |
| other Total, other adverse events | 43 / 55 |
| serious Total, serious adverse events | 4 / 55 |
Outcome results
Primary
To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Population: Responses were calculated by total enrolled to each group by histologic subtype.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Differentiated | Complete Response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Differentiated | Partial response | 16 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Differentiated | Stable Disease | 22 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Differentiated | Progressive Disease | 1 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Differentiated | Not Evaluable for Response | 5 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Poorly Differenitated | Complete Response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Poorly Differenitated | Partial response | 2 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Poorly Differenitated | Stable Disease | 1 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Poorly Differenitated | Progressive Disease | 1 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Poorly Differenitated | Not Evaluable for Response | 2 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Medullary | Complete Response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Medullary | Partial response | 1 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Medullary | Stable Disease | 2 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Medullary | Progressive Disease | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Medullary | Not Evaluable for Response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Anaplastic | Complete Response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Anaplastic | Partial response | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Anaplastic | Stable Disease | 0 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Anaplastic | Progressive Disease | 1 Participants |
| Sorafenib | To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Anaplastic | Not Evaluable for Response | 1 Participants |
Secondary
Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib).
This is the result of the Kaplan Meier analysis of all patients treated with sorafenib
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Population: Of the 59 patients that were consented, four patients were deemed ineligible as a result of inadequate CBC and the establishment of an alternative diagnosis resulting from secondary pathology review. Therefore the total number of patients analyzed going forward was 55.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib | Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib). | 77 weeks |