Phase 2 of Sunitinib (Sutent) in Patients With Locally Advanced or Metastatic Anaplastic, Differentiated or Medullar Thyroid Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 71
- 试验地点
- 30
- 主要终点
- Objective response rate (ORR) : defined as the proportion of patients with confirmed complete (CR) or partial response (PR) according to the RECIST, relative to the total patients enrolled who received at least 1 dose of trial medication
研究概览
简要总结
Due to arguments showing that angiogenesis could be involved in progression of metastatic thyroid carcinoma and to objective response during previous studies with sunitinib (an angiogenic oncology drug also known as Sutent), this study, THYSU, is justified to evaluate the efficacy of sunitinib in metastatic thyroid carcinoma. Furthermore, the standard treatment of metastatic thyroid carcinoma when a general treatment is to be prescribed is limited to radioiodine. When radioiodine becomes ineffective, there is no standard treatment despite some use of chemotherapy.
The objective of the trial is to determine the objective tumor response rate (efficacy) in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma treated with sunitinib; a secondary objective is to evaluate the safety of sunitinib in these patients.
The THYSU trial is a phase II, French multi-center study. This trial's plan is to enroll 75 patients with locally advanced or metastatic anaplastic, differentiated or medullar thyroid carcinoma.
详细描述
The THYSU trial is a phase II trial of sunitinib (Sutent) in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma.
Due to arguments showing that angiogenesis could be involved in progression of metastatic thyroid carcinoma and to objective response during a phase I trial with sunitinib, it was justified to evaluate in a prospective trial the efficacy of sunitinib in metastatic thyroid carcinoma. Furthermore, the standard treatment of metastatic thyroid carcinoma when a general treatment is to be prescribed is limited to radioiodine. When radioiodine becomes ineffective, there is no standard treatment despite some usage of chemotherapy.
The objective of the trial is to determine the objective tumor response rate in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma treated with sunitinib, a secondary objective is to evaluate the safety of sunitinib in these patients with thyroid carcinoma.
The treatment of sunitinib is the standard dosage and schedule. Sunitinib is given orally at the dose of 50 mg daily for 28 days followed by 2 weeks of rest. Forthcoming cycles remain identical. Modification of the dose may use a lower dose at 37.5 mg or 25 mg given daily on the same schedule. All patients will receive repeated cycles of treatment until disease progression, occurrence of unacceptable toxicity, withdrawal of patient consent, or other withdrawal criteria are met. After discontinuation of treatment and the mandated 28-day follow up, patients will be followed only in order to collect information on further antineoplastic therapy and survival. In patients discontinuing treatment for reasons other than disease progression, tumor assessment will continue until disease progression, or initiation of other antineoplastic therapies.
The more frequent side effects are asthenia, mucositis, arterial hypertension, hand foot syndrome and diarrhea. Other side effects have been reported including nausea, vomiting, cutaneous events, decrease in left ventricular ejection fraction, neutropenia, and thrombopenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Patients must have a life expectancy of at least 3 months
- •Patients must have a Karnofsky performance status ≥ 70%
- •Patients must have histologically confirmed thyroid cancer (TC)
- •Tumor disease must be progressive (evidence of disease progression within 6 months before starting the study for follicular and medullary thyroid cancer or symptomatic disease)
- •Patients should not be candidates for surgical resection, external beam radiotherapy or radioiodine
- •Patients must have measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST), such as at least one lesion at least 2 cm in length by conventional computed tomography (CT) techniques or at least 1 cm by spiral CT scan
- •Patients must not have more than one previous systemic treatment for cancer
- •Resolution of all acute toxic effects of any prior local treatment to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 3.0) grade < 1
- •Patients must have discontinued from radiation therapy at least 4 weeks before start of study treatment and must have recovered from any toxic effects of treatment
- •Blood pressure < 140 / 90 mmHg
- •Patients must have adequate organ function defined as: Platelets > 100 x 10*9/L, Hemoglobin > 8 g/dl, ANC > 1.5 x 10*9/L, Bilirubin < 3 mg/dL, AST and ALT < 2.5 x the upper limit of normal (ULN) or < 5 x the ULN for liver metastases, INR < 1.7 or prothrombin time < 6 sec over ULN, Serum creatinine < 1.5 x ULN
- •Patients with reproductive potential must use medically acceptable contraceptive methods (oral contraception or an intrauterine device [IUD])
- •Willingness and ability to comply with all study procedures
- •Affiliated or profit patient of a social security system
排除标准
- •Prior treatment on sunitinib or other anti-angiogenic therapy
- •NCI CTCAE grade 3 hemorrhage < 4 weeks of starting study treatment
- •Diagnosis of any second malignancy < 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months
- •History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
- •Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism
- •Ongoing cardiac dysrhythmias of NCI CTCAE grade > 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females
- •Left ventricular ejection fraction ( LVEF) < 50%
- •Hypertension that cannot be controlled by medications
- •Treatment with anticoagulant agents and treatment with therapeutic doses of warfarin currently or within 2 weeks prior to first day of sunitinib administration
- •Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea
- •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
- •Pregnancy or breastfeeding
- •Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
- •Receipt of any investigational agent prior to study entry
- •Current treatment on another therapeutic clinical trial
- •Patient under safeguard of justice
研究组 & 干预措施
Sunitinib
Sunitinib will be administered orally daily for 4 weeks followed by a 2-week rest; the daily starting dose will be 50 mg with a provision for dose reduction based on tolerability. All patients will receive repeated cycles until disease progression or occurrence of severe toxicity.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Objective response rate (ORR) : defined as the proportion of patients with confirmed complete (CR) or partial response (PR) according to the RECIST, relative to the total patients enrolled who received at least 1 dose of trial medication
时间窗: Every two cycles
次要结局
- Evaluate the safety of sunitinib in patients with thyroid carcinoma(After each cycle of treatment)
- Determine time-to-event variables of overall survival, time to: disease progression, response, and duration of response(variable)