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

Randomized Phase II Study of Sorafenib With or Without Everolimus in Patients With Radioactive Iodine Refractory Hurthle Cell Thyroid Cancer

Status
Active, not recruiting
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02143726
Enrollment
35
Registered
2014-05-21
Start date
2014-10-09
Completion date
2028-08-06
Last updated
2026-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Refractory Hurthle Cell Thyroid Cancer

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.

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.

Interventions

DRUGsorafenib

Given PO

DRUGeverolimus

Given PO

Sponsors

Alliance for Clinical Trials in Oncology
Lead SponsorOTHER
National Cancer Institute (NCI)
CollaboratorNIH
Novartis
CollaboratorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion 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.

Design outcomes

Primary

MeasureTime frameDescription
Progression Free Survival4 years and 4 monthsProgression Free Survival (PFS) was defined as the time from randomization to the first of either disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary

MeasureTime frameDescription
Confirmed Response Rate4 years 4 monthsA patient will be classified as a confirmed response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.
Overall Survival5 years
Number of Participants With Grade 3 or Higher Adverse Events4 years 3 monthsThe maximum grade for each type of adverse event will be summarized using CTCAE version 4.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms.

Countries

United States

Contacts

STUDY_CHAIREric Sherman, M.D.

Memorial Sloan Kettering Cancer Center

Participant flow

Participants by arm

ArmCount
Arm 1 (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.
16
Arm 2 (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.
17
Total33

Baseline characteristics

CharacteristicArm 2 (Sorafenib and Everolimus)TotalArm 1 (Sorafenib)
Age, Continuous65.6 years
STANDARD_DEVIATION 7.4
65.5 years
STANDARD_DEVIATION 10.6
65.4 years
STANDARD_DEVIATION 13.4
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
16 Participants30 Participants14 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants3 Participants2 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants2 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants4 Participants2 Participants
Race (NIH/OMB)
White
15 Participants27 Participants12 Participants
Sex: Female, Male
Female
2 Participants8 Participants6 Participants
Sex: Female, Male
Male
15 Participants25 Participants10 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
5 / 178 / 17
other
Total, other adverse events
17 / 1717 / 17
serious
Total, serious adverse events
10 / 176 / 17

Outcome results

Primary

Progression Free Survival

Progression Free Survival (PFS) was defined as the time from randomization to the first of either disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame: 4 years and 4 months

ArmMeasureValue (MEDIAN)
Arm 1 (Sorafenib)Progression Free Survival9.4 Months
Arm 2 (Sorafenib and Everolimus)Progression Free Survival24.7 Months
p-value: 0.091895% CI: [0.23, 1.33]Log Rank
Secondary

Confirmed Response Rate

A patient will be classified as a confirmed response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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: 4 years 4 months

ArmMeasureValue (NUMBER)
Arm 1 (Sorafenib)Confirmed Response Rate0.188 Proportion of participants
Arm 2 (Sorafenib and Everolimus)Confirmed Response Rate0.235 Proportion of participants
Secondary

Number of Participants With Grade 3 or Higher Adverse Events

The maximum grade for each type of adverse event will be summarized using CTCAE version 4.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms.

Time frame: 4 years 3 months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Arm 1 (Sorafenib)Number of Participants With Grade 3 or Higher Adverse Events10 Participants
Arm 2 (Sorafenib and Everolimus)Number of Participants With Grade 3 or Higher Adverse Events12 Participants
Secondary

Overall Survival

Time frame: 5 years

ArmMeasureValue (MEDIAN)
Arm 1 (Sorafenib)Overall SurvivalNA Months
Arm 2 (Sorafenib and Everolimus)Overall Survival40.1 Months
p-value: 0.397695% CI: [0.53, 4.96]Log Rank

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026