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Sorafenib Tosylate With or Without Everolimus in Treating Patients With Advanced, Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer

NCT02143726

Description:

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.

Related Conditions:
  • Thyroid Gland Oncocytic Follicular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sorafenib Tosylate With or Without Everolimus in Treating Patients With Advanced, Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer
  • Official Title: Randomized Phase II Study of Sorafenib With or Without Everolimus in Patients With Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: A091302
  • SECONDARY ID: U10CA180821
  • SECONDARY ID: NCI-2014-00623
  • NCT ID: NCT02143726

Conditions

  • Refractory Hurthle Cell Thyroid Cancer

Interventions

DrugSynonymsArms
sorafenibNexavar ®, BAY 43-9006sorafenib
everolimusRAD001, Afinitor ®sorafenib and everolimus

Purpose

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.

Detailed Description

      This randomized Phase II trial will compare the progression-free survival (PFS) of sorafenib
      and everolimus versus sorafenib alone in patients with radioactive iodine refractory hurthle
      cell thyroid cancer. Prior studies have shown that the median PFS is generally around 4.5
      months for sorafenib alone in this disease population. It is hoped that the combination of
      everolimus and sorafenib can increase the median PFS to at least 9 months. In addition to
      PFS, this trial will also compare the confirmed response rate, overall survival (OS) and
      adverse event rates between sorafenib and everolimus vs. sorafenib alone. The primary and
      secondary objectives for the study are listed below.

      Primary Objective:

      To compare the progression free survival between sorafenib and everolimus versus sorafenib
      alone in patients with radioactive iodine refractory Hurthle cell thyroid cancer

      Secondary Objective:

      To compare the confirmed response rate, overall survival and adverse event rates between
      sorafenib and everolimus versus sorafenib alone.

      Treatment will continue until disease progression or unacceptable adverse events. Patients
      will be followed for 5 years after randomization.
    

Trial Arms

NameTypeDescriptionInterventions
sorafenibActive ComparatorPatients receive sorafenib 400 mg PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over and receive everolimus 10 mg PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • sorafenib
sorafenib and everolimusExperimentalPatients receive sorafenib 400 mg PO twice daily and everolimus 5 mg PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • sorafenib
  • everolimus

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:Up to 5 years post-randomization
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Confirmed response rate
Time Frame:Up to 5 years post-randomization
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 5 years post-randomization
Safety Issue:
Description:
Measure:Incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events
Time Frame:Up to 5 years post-randomization
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

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