Sorafenib Tosylate With or Without Everolimus in Treating Patients With Advanced, Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer
Condition: Refractory Hurthle Cell Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: sorafenib; everolimus
Intervention description: Given PO; Given PO
Intervention MeSH terms: Everolimus; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the effects, good and bad, of using everolimus along
      with sorafenib tosylate versus sorafenib tosylate alone in treating patients with advanced
      radioactive iodine refractory thyroid cancer. Sorafenib tosylate and everolimus may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of
      everolimus to sorafenib tosylate may cause more shrinkage of thyroid cancer and may prevent
      it from growing but it could also cause more side effects than sorafenib tosylate alone. It
      is not yet known whether this treatment with sorafenib tosylate and everolimus is better, the
      same, or worse than sorafenib tosylate alone.
    

Eligibility criteria:

        Eligibility Criteria:

          1. Central pathology review submission - Patients must have 10 representative hematoxylin
             and eosin (H&E) stained thyroid tissue slides OR tumor block available for submission
             to central pathology review. This review is mandatory prior to registration to confirm
             eligibility.

          2. Measurable disease - Patients must have measurable disease by Response Evaluation
             Criteria In Solid Tumors (RECIST) criteria, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as ≥
             20 mm with conventional techniques or as ≥ 10 mm with spiral computed tomography (CT)
             scan. CT must be performed within 28 days of registration.

          3. Radioactive iodine (RAI) - refractory disease defined as 1 or more of the following:

               -  Patients who have received greater than 600 mCi of radioactive iodine in their
                  lifetime OR

               -  RAI-avid metastatic lesion which remained stable in size or progressed despite
                  RAI treatment within 9 months of RAI treatment OR

               -  10% or more increase in serum thyroglobulin (on thyroid-stimulating hormone
                  [TSH]-suppression) within 9 months of RAI treatment OR

               -  Index metastatic lesion non-RAI avid on a diagnostic RAI scan OR

               -  Presence of fluorodeoxyglucose (FDG) avid metastatic lesions on positron emission
                  tomography (PET)/CT scan (standardized uptake values [SUV]max > 5 of any single
                  lesion)

          4. Progressive disease defined by RECIST criteria ≤ 14 months

          5. Patients must have metastatic disease or locally advanced unresectable disease

          6. Prior treatment

               -  Patients may have received prior radiation therapy to index lesions ≥ 28 days
                  prior to registration on this protocol if there has been documented progression
                  by RECIST criteria. Prior radiation therapy to the non-index lesions is allowed
                  if ≥ 28 days prior to registration on this protocol.

               -  Prior RAI therapy is allowed if ≥ 90 days prior to registration on this protocol
                  and evidence of progression (as defined above) has been documented in the interim
                  (a diagnostic study using < 10 mCi of RAI is not considered RAI therapy).

               -  Prior chemotherapy is allowed if ≥ 28 days prior to registration on this
                  protocol.

               -  Patient may have received any number of prior lines of therapy.

               -  No prior use of sorafenib or an mammalian target of rapamycin (mTOR) (including
                  phosphoinositide 3-kinase [PI3k] or protein kinase B [AKT]) inhibitor for the
                  treatment of thyroid cancer.

          7. No history of major surgery ≤ 28 days of registration

          8. No history of intracranial brain metastasis

          9. Cardiovascular disease. No history of any of the following ≤ 6 months of registration:

               -  Myocardial infarction or unstable angina

               -  New York Heart Association grade III or greater congestive heart failure

               -  Cerebrovascular accident

               -  Grade 3 or 4 peripheral ischemia

               -  Grade 3 or 4 thromboembolic event

         10. Liver disease: No history of the following:

               -  Child Pugh Class B or C liver disease

               -  "Chronic active" hepatitis defined as:

                    1. Hepatitis B surface antigen (HBsAg) > 6 months

                    2. Serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) 20,000 IU/ml (105
                       copies/ml), lower values 2,000-20,000 IU/ml (104-105 copies/ml) are often
                       seen in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B

                    3. Persistent or intermittent elevation in alanine aminotransferase
                       (ALT)/aspartate aminotransferase (AST) levels

                    4. Liver biopsy showing chronic hepatitis with moderate or severe
                       necroinﬂammation

         11. No history of gastrointestinal fistula or gastrointestinal perforation < 90 days of
             registration.

         12. No known history of prolonged QT syndrome

         13. No Grade 3 or 4 hypertension (systolic blood pressure [BP] >160 and or diastolic BP >
             100) that cannot be controlled with medication prior to registration.

         14. Concomitant medications:

               -  Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4
                  (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must
                  discontinue the drug for 14 days prior to registration on the study.

               -  Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
                  Patients must discontinue the drug 14 days prior to the start of study treatment.

               -  Patients requiring anticoagulation must be on stable dose of medication prior to
                  registration.

         15. Not pregnant and not nursing, because this study involves an investigational agent
             whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
             are unknown. Therefore, for women of childbearing potential only, a negative serum
             pregnancy test done ≤ 7 days prior to registration is required.

         16. Age ≥ 18 years

         17. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

         18. Required Initial Laboratory Values:

               -  Absolute neutrophil count (ANC) ≥ 1,500/mm^3

               -  Platelet count ≥ 100,000/mm^3

               -  Creatinine ≤ 1.5 mg/dL OR

               -  Calculated creatinine clearance ≥ 30 mL/min

               -  Total bilirubin ≤ 1.5 x upper limits of normal (ULN)

               -  Serum glutamic oxaloacetic transaminase (SGOT) (AST) ≤ 2.5 x ULN

               -  Fasting serum cholesterol ≤ 300 mg/dL

         19. Documentation of disease: Histologic Documentation - Eligible patients must have
             histopathologically confirmed Hürthle cell thyroid cancer by central review.