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
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.
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.
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 →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.
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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):
Exclusion Criteria:
Patients with any of the following conditions are excluded:
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
Optional correlative studies
Optional correlative studies
Also known as: PHARMACOGENOMIC
Given PO
Given PO
Also known as: SU 011248, SU 11248, SU-011248, SU-11248, SU011248, SU11248, sunitinib, Sutent
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
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
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
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
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
| Milestone | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Started | 38 | 25 |
| Completed | 38 | 23 |
| Not completed | 0 | 2 |
| Withdrew: Withdrawal by subject | 0 | 2 |
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."
| Participants | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Objective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) | 9 | 7 |
Any grade toxicity of any type, regardless of attribution
| Participants | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Incidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.0 | 38 | 24 |
Kaplan-Meier curves will be generated and 95% confidence intervals will be derived for median overall survival.
| Months | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Overall Survival | 32.6 (18.4 to 70.9) | 65.4 (27.0 to 69.5) |
| Months | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Time to Progression or Death Evaluated Using the RECIST | 12.8 (8.3 to 16.4) | 19.3 (7.7 to 34.6) |
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.
Results for this outcome have not been posted.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sunitinib Malate-Radioactive Iodine Refractory Subgroup | 21/38 (55.3%) | 17/38 (44.7%) | 38/38 (100%) |
| Sunitinib Malate-Metastatic Medullary Subgroup | 5/25 (20%) | 12/25 (48%) | 24/25 (96%) |
| Event | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| Abdominal painGastrointestinal disorders | 0/38 | 2/25 |
| AnorexiaMetabolism and nutrition disorders | 0/38 | 2/25 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 0/38 | 2/25 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 2/38 | 2/25 |
| DehydrationMetabolism and nutrition disorders | 2/38 | 1/25 |
| Hepatic failureHepatobiliary disorders | 2/38 | 0/25 |
| Left ventricular systolic dysfunctionCardiac disorders | 2/38 | 0/25 |
| Bone painMusculoskeletal and connective tissue disorders | 0/38 | 1/25 |
| Bronchial obstructionRespiratory, thoracic and mediastinal disorders | 0/38 | 1/25 |
| Buttock painMusculoskeletal and connective tissue disorders | 0/38 | 1/25 |
| Event | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup |
|---|---|---|
| FatigueGeneral disorders | 33/38 | 18/25 |
| White blood cell decreasedInvestigations | 30/38 | 19/25 |
| AnemiaBlood and lymphatic system disorders | 29/38 | 14/25 |
| HyperglycemiaMetabolism and nutrition disorders | 27/38 | 17/25 |
| DiarrheaGastrointestinal disorders | 25/38 | 11/25 |
| Platelet count decreasedInvestigations | 22/38 | 12/25 |
| Lymphocyte count decreasedInvestigations | 20/38 | 14/25 |
| Neutrophil count decreasedInvestigations | 21/38 | 8/25 |
| NauseaGastrointestinal disorders | 20/38 | 13/25 |
| Mucositis oralGastrointestinal disorders | 18/38 | 12/25 |
| Age, Continuous(years) | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup | Total |
|---|---|---|---|
| Mean | 59.1 (37 to 76) | 50.9 (23 to 73) | 55.8 (23 to 76) |
| Sex: Female, Male(Participants) | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup | Total |
|---|---|---|---|
| Female | 14 | 12 | 26 |
| Male | 24 | 13 | 37 |
| Race (NIH/OMB)(Participants) | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 4 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 37 | 20 | 57 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Sunitinib Malate-Radioactive Iodine Refractory Subgroup | Sunitinib Malate-Metastatic Medullary Subgroup | Total |
|---|---|---|---|
| United States | 38 | 25 | 63 |
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National Cancer Institute (NCI)