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

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ClinicalTrials.gov Identifier: NCT02143726
Recruitment Status : Recruiting
First Posted : May 21, 2014
Last Update Posted : July 17, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Novartis
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief 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.

Condition or disease Intervention/treatment Phase
Refractory Hurthle Cell Thyroid Cancer Drug: sorafenib Drug: everolimus Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Sorafenib With or Without Everolimus in Patients With Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer
Study Start Date : October 2014
Estimated Primary Completion Date : August 2020


Arm Intervention/treatment
Active Comparator: sorafenib
Patients 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.
Drug: sorafenib
Given PO
Other Name: Nexavar ®, BAY 43-9006

Experimental: sorafenib and everolimus
Patients 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.
Drug: sorafenib
Given PO
Other Name: Nexavar ®, BAY 43-9006

Drug: everolimus
Given PO
Other Name: RAD001, Afinitor ®




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 5 years post-randomization ]

Secondary Outcome Measures :
  1. Confirmed response rate [ Time Frame: Up to 5 years post-randomization ]
  2. Overall survival [ Time Frame: Up to 5 years post-randomization ]
  3. Incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events [ Time Frame: Up to 5 years post-randomization ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02143726


Contacts
Contact: Eric Sherman, M.D. 646 888-4234

Locations
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Ashish V. Chintakuntlawar    855-776-0015      
Principal Investigator: Ashish V. Chintakuntlawar         
United States, Illinois
Northwestern University Suspended
Chicago, Illinois, United States, 60611
United States, Iowa
Siouxland Regional Cancer Center Recruiting
Sioux City, Iowa, United States, 51101
Contact: Donald B. Wender    712-252-0088      
Principal Investigator: Donald B. Wender         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Francis P. Worden    800-865-1125      
Principal Investigator: Francis P. Worden         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Ashish V. Chintakuntlawar    855-776-0015      
Principal Investigator: Ashish V. Chintakuntlawar         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Yungpo B. Su    402-354-5144      
Principal Investigator: Yungpo B. Su         
United States, New Jersey
Memorial Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
Memorial Sloan Kettering Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Eric J. Sherman    212-639-7592      
Principal Investigator: Eric J. Sherman         
Memorial Sloan Kettering Sleepy Hollow Suspended
Sleepy Hollow, New York, United States, 10591
United States, North Carolina
Southeastern Medical Oncology Center-Clinton Recruiting
Clinton, North Carolina, United States, 28328
Contact: James N. Atkins    919-587-9077    ecooke@cancersmoc.com   
Principal Investigator: James N. Atkins         
Southeastern Medical Oncology Center-Goldsboro Recruiting
Goldsboro, North Carolina, United States, 27534
Contact: James N. Atkins    919-587-9077    ecooke@cancersmoc.com   
Principal Investigator: James N. Atkins         
Wayne Memorial Hospital Recruiting
Goldsboro, North Carolina, United States, 27534
Contact: James N. Atkins    919-731-6687    ecooke@cancersmoc.com   
Principal Investigator: James N. Atkins         
Southeastern Medical Oncology Center-Jacksonville Recruiting
Jacksonville, North Carolina, United States, 28546
Contact: James N. Atkins    910-353-0824    ecooke@cancersmoc.com   
Principal Investigator: James N. Atkins         
Southeastern Medical Oncology Center-Wilson Suspended
Wilson, North Carolina, United States, 27893
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Bhavana Konda    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Bhavana Konda         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Jessica R. Bauman    215-728-4790      
Principal Investigator: Jessica R. Bauman         
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Novartis
Investigators
Study Chair: Eric Sherman, M.D. Memorial Sloan Kettering Cancer Center

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT02143726     History of Changes
Other Study ID Numbers: A091302
U10CA180821 ( U.S. NIH Grant/Contract )
NCI-2014-00623 ( Registry Identifier: NCI Clinical Trials Reporting Office )
First Posted: May 21, 2014    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Thyroid Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Everolimus
Sirolimus
Thyroid Diseases
Endocrine System Diseases
Sorafenib
Niacinamide
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances