Return to List

Study Summary
No. 2007-0526:.......Thyroid......Naifa L. Busaidy......Endocrine Neoplasia & Hormonal Disorders
.
Study Summary Title
Study Summary
Number:
2007-0526
Study Title:Phase II trial of Sunitinib (SU11248) in Iodine-131 refractory, Unresectable
differentiated thyroid cancers and medullary thyroid cancers
.
Physician New Patient Referral
Name:Naifa L. BusaidyPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Endocrine Neoplasia & Hormonal DisordersReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2841
Contact us about clinical trials
.
General Information
Disease Group:ThyroidSupported By:N.C.I.
N.C.I.
Phase of Study:Phase IIReturn
Visit:
Weekly Vital Signs during the first 6 weeks on drug, then Visits per protocol
are every 6 weeks with RECIST evaluation every 12 weeks
Treatment
Agents:
Sunitinib MalateHome Care:Medication will be given orally daily. Patients will take drug in the morning
for 4 weeks and then be off for 2 weeks this will equate a cycle
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if sunitinib can help
control thyroid cancer that has spread outside the thyroid. The safety of this
drug will also be studied.
.
Study Objectives / Outcomes
Primary Objective:

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


Secondary Objectives:
1. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with WDTC or MTC treated with single agent sunitinib.
2. Determine whether the presence of RET gene rearrangements in patients with WDTC or RET mutations in patients with MTC predict response to sunitinib.
3. Determine whether therapy with sunitinib affects phosphorylation of downstream RET effector, ERK, in WDTC and MTC tissue.
4. Determine whether specific germ-line polymorphisms in the RET gene are associated with favorable outcome in patients with WDTC treated with sunitinib.
.
Study Status Information
Study Activation / Registration Date:08/18/2008
IRB Review and Approval Date:03/14/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:60 (25 Differentiated and 35 Medullary Thyroid Cancer patients
.
Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) 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.

2) 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 CT scan. Biochemically measurable disease is defined as an elevated thyroglobulin (WDTC patients) or calcitonin (MTC patients).

3) Patients must have evidence of disease progression (objective growth of existing tumors or rising thyroglobulin or calcitonin levels) within the last 6 months.

4) 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).

5) Because no dosing or adverse event data are currently available on the use of sunitinib in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.

6) Patients must have normal organ and marrow function as defined below: 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 AST(SGOT)/ALT(SGPT) </=2.5 X institutional ULN creatinine within normal institutional limits OR creatinine clearance >/=60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

7) Patients must have QTc < 500 msec.

8) The following groups of patients are eligible provided they have New York Heart Association Class II (NYHA) cardiac function on baseline ECHO/MUGA: a)those with a history of Class I heart failure who are asymptomatic on treatment b)with prior anthracycline c)received central thoracic radiation that included the heart in the radiotherapy port.

9) The effects of sunitinib on the developing human fetus at therapeutic dose are unknown. For this reason and because antiangiogenic agents are known to be teratogenic, women 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.

10) Ability to understand and the willingness to sign a written informed consent document.

11) Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial.

12) ECOG performance status 0 - 2 (Karnofsky = / > 60%)

13) Life expectancy greater than 12 weeks.

Exclusion Criteria:1) 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.

2) At least 4 weeks must have elapsed since any major surgery.

3) Patients may not be receiving any other investigational agents

4) Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, VEGF Trap, etc.).

5) History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.

6) 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 ECG abnormalities are excluded.

7) Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible.

8) 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 PT INR is </=1.5.

9) Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded.

10) Patients with any of the following conditions are excluded: • Serious or non-healing wound, non-healing ulcer, or non-healing bone fracture. • History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days of treatment. • Any history of CVA or TIA within 12 months prior to study entry. classification system 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.

11) Continued from # 10 History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within past 12 months • History of pulmonary embolism within the past 12 months. • Class III or IV heart failure as defined by the NYHA functional

12) 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. A comprehensive list of medications and substances known or with the potential to alter the pharmacokinetics of sunitinib through CYP3A4.

13) Patients with known brain mets should be excluded because of poor prognosis & because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic & other adverse events. Patients with treated brain metastases 8 weeks out of therapy are allowed. Patients can't be receiving enzyme inducing anti-convulsants including carbamazepine, phenobarbital, and phenytoin.

14) 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.

15) 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.

16) 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.

17) Patients with conditions classified as NYHA III or IV per the New York Heart Association Classifications

18) Patients with an ejection fraction of < 40%

.
Links
Registration Number: NCT00381641
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center