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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00381641
First received: September 26, 2006
Last updated: March 18, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Papillary Thyroid Cancer
Recurrent Thyroid Cancer
Stage III Follicular Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Thyroid Gland Medullary Carcinoma
Drug: sunitinib malate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate, assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of toxicity, graded according to the Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: From time of first treatment with sunitinib, assessed up to 2 years ] [ Designated as safety issue: Yes ]
  • Time to progression evaluated using the RECIST [ Time Frame: Time from start of treatment to time of progression or death of any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be generated and 90% confidence intervals will be derived for median progression-free and overall survival.


Other Outcome Measures:
  • Changes in laboratory correlates analyzed using paired t-tests [ Time Frame: Baseline to 2 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 60
Study Start Date: August 2006
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sunitinib malate)
Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Optional correlative studies
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies

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. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Χ 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
  • 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:

  • 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
  • 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; 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; breastfeeding should be discontinued if the mother is treated with sunitinib malate
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00381641

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Evanston CCOP-NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology-Hematology Associates Limited
Joliet, Illinois, United States, 60435
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States, 46845
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46628
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Oncology Care Associates PLLC
Saint Joseph, Michigan, United States, 49085
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Investigators
Principal Investigator: Jonas DeSouza University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00381641     History of Changes
Other Study ID Numbers: NCI-2009-00213, NCI-2009-00213, NCI-7735, CDR0000502260, UCCRC-14696A, 14696A, 7735, N01CM62202, N01CM62201, P30CA014599
Study First Received: September 26, 2006
Last Updated: March 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Thyroid Neoplasms
Thyroid Diseases
Adenocarcinoma, Follicular
Carcinoma, Medullary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Adenocarcinoma
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Nerve Tissue
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014