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CompletedNCT00381641Updated Mar 28, 2025Results posted

Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

A Phase 2 interventional study of Laboratory Biomarker Analysis and Pharmacogenomic Study in Differentiated Thyroid Gland Carcinoma, Recurrent Thyroid Gland Carcinoma and Refractory Thyroid Gland Carcinoma, sponsored by National Cancer Institute (NCI). Completed at 17 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-28.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
63
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial studies how well sunitinib malate works in treating patients with thyroid cancer that did not respond to iodine I 131 (radioactive iodine) and cannot be removed by surgery. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Read the detailed description

PRIMARY OBJECTIVES:

I. Determine the response rate of single agent sunitinib (sunitinib malate) in patients with iodine refractory, unresectable well-differentiated thyroid cancer (WDTC) who have evidence of disease progression within 6 months of study enrollment.

II. Determine the response rate of single agent sunitinib in patients with medullary thyroid cancer (MTC) who have evidence of disease progression within 6 months of study enrollment.

III. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with WDTC or MTC treated with single agent sunitinib.

IV. Determine whether the presence of ret proto-oncogene (RET) gene rearrangements in patients with WDTC or RET mutations in patients with MTC predict response to sunitinib.

V. Determine whether therapy with sunitinib affects phosphorylation of downstream RET effector, mitogen-activated protein kinase 1 (ERK), in WDTC and MTC tissue.

VI. Determine whether specific germ-line polymorphisms in the RET gene are associated with favorable outcome in patients with WDTC treated with sunitinib.

OUTLINE: Patients are assigned to 1 of 2 cohorts according to type of thyroid cancer (medullary vs well-differentiated).

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

02

Conditions studied

  • Differentiated Thyroid Gland Carcinoma
  • Recurrent Thyroid Gland Carcinoma
  • Refractory Thyroid Gland Carcinoma
  • Stage III Thyroid Gland Follicular Carcinoma AJCC v7
  • Stage III Thyroid Gland Medullary Carcinoma AJCC v7
  • Stage IV Thyroid Gland Follicular Carcinoma AJCC v7
  • Stage IV Thyroid Gland Medullary Carcinoma AJCC v7
  • Stage IV Thyroid Gland Papillary Carcinoma AJCC v7
  • Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7
  • Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7
  • Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7
  • Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7
  • Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7
  • Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7
  • Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7
  • Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7
  • Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7
  • Thyroid Gland Oncocytic Carcinoma
  • Unresectable Thyroid Gland Carcinoma
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 63 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients must have histologically or cytologically confirmed papillary, follicular, or Hurthle cell carcinoma (cohort A) or medullary thyroid carcinoma (cohort B); their disease must have progressed despite treatment with iodine-131 therapy or they are not candidates for iodine-131 therapy and their disease cannot be completely removed by surgery; all patients with WDTC are expected to be on thyroxine suppression therapy
  • Patients must have radiographically or biochemically measurable disease; radiographically measurable disease is 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; biochemically measurable disease is defined as an elevated thyroglobulin (WDTC patients) or calcitonin (MTC patients)
  • Patients must have evidence of disease progression (objective growth of existing tumors or rising thyroglobulin or calcitonin levels) within the last 6 months
  • Patients cannot have received prior receptor tyrosine kinase inhibitors; patients cannot have received more than one prior chemotherapy regimen for metastatic disease; patients cannot have received prior external beam radiation to the measured tumor constituting the target lesion(s)
  • Life expectancy of greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Serum calcium =\< 12.0 mg/dL
  • Total serum bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 2.5 X institutional upper limit of normal OR =\< 5 X institutional upper limit of normal if patient has liver metastases
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
  • Patients must have corrected QT interval (QTc) \< 500 msec
  • The following groups of patients are eligible provided they have New York Heart Association class II (NYHA) cardiac function on baseline echocardiogram (ECHO)/multigated acquisition scan (MUGA):

    • Those with a history of class II heart failure who are asymptomatic on treatment
    • Those with prior anthracycline exposure
    • Those who have received central thoracic radiation that included the heart in the radiotherapy port
  • The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because antiangiogenic agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery
  • Patients may not be receiving any other investigational agents
  • Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, vascular endothelial growth factor [VEGF] Trap, etc.)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib
  • Patients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec), serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia greater than or equal to 3 beats in a row) or other significant electrocardiogram (ECG) abnormalities are excluded
  • Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible
  • Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =\< 1.5
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded
  • Patients with any of the following conditions are excluded:

    • Serious or non-healing wound, ulcer, or bone fracture
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
    • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
    • History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
    • History of pulmonary embolism within the past 12 months
    • Class III or IV heart failure as defined by the NYHA functional classification system
  • Because sunitinib is metabolized primarily by the CYP3A4 liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications, particularly patients with gliomas or brain metastases who are taking enzyme-inducing anticonvulsant agents
  • Patients with known brain metastases should be excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; N.B.: Patients with brain metastases with stable neurologic status following local therapy (surgery or radiation) for at least 8 weeks from definitive therapy and without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events are eligible for participation; patients cannot be receiving enzyme inducing anti-convulsants including carbamazepine, phenobarbital, and phenytoin
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
  • Pregnant women are excluded from this study because sunitinib is an antiangiogenic agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib, breastfeeding should be discontinued if the mother is treated with sunitinib malate
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients with conditions classified as NYHA III or IV per the New York Heart Association classifications
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
63 participants (actual)

Study arms

  • Experimental
    Treatment (sunitinib malate)

    Patients receive sunitinib malate PO QD on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

    Other: Laboratory Biomarker Analysis · Other: Pharmacogenomic Study · Drug: Sunitinib · Drug: Sunitinib Malate

Interventions

  • OtherLaboratory Biomarker Analysis

    Optional correlative studies

  • OtherPharmacogenomic Study

    Optional correlative studies

    Also known as: PHARMACOGENOMIC

  • DrugSunitinib

    Given PO

  • DrugSunitinib Malate

    Given PO

    Also known as: SU 011248, SU 11248, SU-011248, SU-11248, SU011248, SU11248, sunitinib, Sutent

06

What researchers measure

Primary outcomes

  1. Objective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or 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: Up to 2 years

Secondary outcomes

  1. Incidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.0

    Any grade toxicity of any type, regardless of attribution

    Time frame: From time of first treatment with sunitinib, assessed up to 2 years

  2. Overall Survival

    Kaplan-Meier curves will be generated and 95% confidence intervals will be derived for median overall survival.

    Time frame: Up to 10 years

  3. Time to Progression or Death Evaluated Using the RECIST

    Time frame: Time from start of treatment to time of progression or death of any cause, assessed up to 10 years

Other outcomes

  1. Changes in Laboratory Correlates Analyzed Using Paired T-tests

    Relevant laboratory correlates will be compared between responders and non-responders using the Wilcoxon rank sum test. The association between the presence or absence of RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorphisms in the RET gene and response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as covariates (univariate analyses only due to the small sample size) in a Cox regression model of progression-free survival.

    Time frame: Baseline to 2 years

07

Results

Posted Sep 15, 2017

Participant flow

Participant flow — Overall Study
MilestoneSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Started3825
Completed3823
Not completed02
Withdrew: Withdrawal by subject02

Outcome measures

PrimaryObjective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or 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:
Up to 2 years
Reported as:
Count of participants · Participants
Objective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST)
ParticipantsSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Objective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST)97
Statistical analysis
  • Sunitinib Malate-Radioactive Iodine Refractory Subgroup vs Sunitinib Malate-Metastatic Medullary Subgroup · Simon, two-stage design · p = <0.10 (For iodine refractory subgroup, null hypothesis could be rejected if 6 or more responses were observed. For metastatic medullary subgroup, null hypothesis could be rejected if 3 or more responses were observed.)
SecondaryIncidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.0

Any grade toxicity of any type, regardless of attribution

Time frame:
From time of first treatment with sunitinib, assessed up to 2 years
Reported as:
Count of participants · Participants
Incidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.0
ParticipantsSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Incidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.03824
SecondaryOverall Survival

Kaplan-Meier curves will be generated and 95% confidence intervals will be derived for median overall survival.

Time frame:
Up to 10 years
Reported as:
Median · Months
Overall Survival
MonthsSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Overall Survival32.6 (18.4 to 70.9)65.4 (27.0 to 69.5)
SecondaryTime to Progression or Death Evaluated Using the RECIST
Time frame:
Time from start of treatment to time of progression or death of any cause, assessed up to 10 years
Reported as:
Median · Months
Time to Progression or Death Evaluated Using the RECIST
MonthsSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Time to Progression or Death Evaluated Using the RECIST12.8 (8.3 to 16.4)19.3 (7.7 to 34.6)
Other pre-specifiedChanges in Laboratory Correlates Analyzed Using Paired T-tests

Relevant laboratory correlates will be compared between responders and non-responders using the Wilcoxon rank sum test. The association between the presence or absence of RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorphisms in the RET gene and response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as covariates (univariate analyses only due to the small sample size) in a Cox regression model of progression-free survival.

Time frame:
Baseline to 2 years

Results for this outcome have not been posted.

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sunitinib Malate-Radioactive Iodine Refractory Subgroup21/38 (55.3%)17/38 (44.7%)38/38 (100%)
Sunitinib Malate-Metastatic Medullary Subgroup5/25 (20%)12/25 (48%)24/25 (96%)
Most frequent serious events
Showing 10 of 40
Most frequent serious events
EventSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
Abdominal painGastrointestinal disorders0/382/25
AnorexiaMetabolism and nutrition disorders0/382/25
DyspneaRespiratory, thoracic and mediastinal disorders0/382/25
PneumonitisRespiratory, thoracic and mediastinal disorders2/382/25
DehydrationMetabolism and nutrition disorders2/381/25
Hepatic failureHepatobiliary disorders2/380/25
Left ventricular systolic dysfunctionCardiac disorders2/380/25
Bone painMusculoskeletal and connective tissue disorders0/381/25
Bronchial obstructionRespiratory, thoracic and mediastinal disorders0/381/25
Buttock painMusculoskeletal and connective tissue disorders0/381/25
Most frequent other events
Showing 10 of 89
Most frequent other events
EventSunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary Subgroup
FatigueGeneral disorders33/3818/25
White blood cell decreasedInvestigations30/3819/25
AnemiaBlood and lymphatic system disorders29/3814/25
HyperglycemiaMetabolism and nutrition disorders27/3817/25
DiarrheaGastrointestinal disorders25/3811/25
Platelet count decreasedInvestigations22/3812/25
Lymphocyte count decreasedInvestigations20/3814/25
Neutrophil count decreasedInvestigations21/388/25
NauseaGastrointestinal disorders20/3813/25
Mucositis oralGastrointestinal disorders18/3812/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary SubgroupTotal
Mean59.1 (37 to 76)50.9 (23 to 73)55.8 (23 to 76)
Sex: Female, Male
Sex: Female, Male(Participants)Sunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary SubgroupTotal
Female141226
Male241337
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary SubgroupTotal
American Indian or Alaska Native000
Asian044
Native Hawaiian or Other Pacific Islander000
Black or African American112
White372057
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Sunitinib Malate-Radioactive Iodine Refractory SubgroupSunitinib Malate-Metastatic Medullary SubgroupTotal
United States382563
08

Study locations

17 sites
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Decatur Memorial Hospital
    Decatur, Illinois 62526, United States
  • NorthShore University HealthSystem-Evanston Hospital
    Evanston, Illinois 60201, United States
  • Ingalls Memorial Hospital
    Harvey, Illinois 60426, United States
  • Duly Health and Care Joliet
    Joliet, Illinois 60435, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • Illinois CancerCare-Peoria
    Peoria, Illinois 61615, United States
  • Central Illinois Hematology Oncology Center
    Springfield, Illinois 62702, United States
  • Southern Illinois University School of Medicine
    Springfield, Illinois 62702, United States
  • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    Fort Wayne, Indiana 46845, United States
  • Northern Indiana Cancer Research Consortium
    South Bend, Indiana 46628, United States
  • University of Maryland/Greenebaum Cancer Center
    Baltimore, Maryland 21201, United States
  • University of Michigan Comprehensive Cancer Center
    Ann Arbor, Michigan 48109, United States
  • Oncology Care Associates PLLC
    Saint Joseph, Michigan 49085, United States
  • Mercy Hospital Saint Louis
    Saint Louis, Missouri 63141, United States
  • M D Anderson Cancer Center
    Houston, Texas 77030, United States
  • Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 28, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00381641
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Sep 28, 2006
Start date
Aug 29, 2006
Primary completion
Dec 31, 2016
Completion
Dec 10, 2024
Results posted
Sep 15, 2017
Last update
Mar 28, 2025

Study contacts

Tanguy Y Seiwert
principal investigator · University of Chicago Comprehensive Cancer Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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