A Investigator Initiated Phase II Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Clinical Benefit Rate (CBR) Which is Defined as Either a Partial Response (PR) Complete Response (CR) or Stable Disease (SD) for ≥ 12 Weeks Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
研究概览
简要总结
This is an open-label phase II study of an investigational drug, sunitinib malate in patients with advanced malignant paraganglioma or phaeochromocytoma cancer. Paragangliomas (PGs) are tumours that arise from the para-sympathetic system in the head and neck and sympathetic system in the thorax and abdomen. Paragangliomas that secrete hormones (catecholamines) from the adrenal glands are called pheochromocytomas (PCs). In this study, patients whose disease has advanced or spread despite prior standard therapy, will receive sunitinib for 4-weeks followed by a 2-week rest period, for up to 12 months, in the absence of disease progression. Sunitinib is an investigational drug, which has been shown to shrink tumours in several tumour models. The study will evaluate the efficacy as well as the toxicity profile of sunitinib when used as an alternative treatment for patients with PG/PC tumours.
详细描述
This study will be a single arm, open-label, phase II trial of sunitinib in patients with metastatic or locally advanced malignant paraganglioma or phaeochromocytoma. Oral sunitinib (50 mg) will be administered to all patients daily for the first four weeks of a six week study cycle, followed by a 2-week rest. Patients will be assessed for response to study treatment using MRI/CT scans as well as bio-chemical tests, and will receive the study treatment for up to 12 months or until disease progression.
Primary study outcomes include:
To assess the efficacy (response rate) of sunitinib given orally daily for 4 out of every 6 weeks in patients with advanced or metastatic paraganglioma/ pheochromocytoma.
To assess the toxicity of sunitinib in patients with advanced or metastatic paraganglioma/ pheochromocytoma.
To document effects of sunitinib on markers of biochemical activity of advanced or metastatic paraganglioma/ pheochromocytoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability.
- •Evidence of recent disease progression (radiological, biochemical, symptomatic).
- •Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by CT scan.
- •Life expectancy of greater than 24 weeks.
- •Age > 18 years.
- •Patients must have normal organ and marrow function.
- •Patients must have PT/INR/PTT within 1.2 X the upper limit
- •Patients may have had prior radiation therapy. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study.
- •Previous Surgery: Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration
- •Laboratory Requirements Parameter Limit granulocytes (AGC) > 1.5 x 109/L platelets > 100 x 109/L bilirubin < 1.5XULN AST and ALT < 2.5 x ULN Amylase <1.5XULN Lipase <1.5XULN Calcium < 3 mmol/L creatinine < 2.0XULN
排除标准
- •History of other malignancies.
- •Patients with known brain metastases.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.
- •Patients receiving concurrent treatment with other anti-cancer therapy given for paraganglioma or pheochromocytoma or other therapy or other investigational anticancer agents.
- •Patients who have received prior treatment with any other antiangiogenic agent or multi-targeted tyrosine kinase inhibitors are ineligible.
- •Patients with any of the following cardiovascular findings are to be excluded:
- •QTc prolongation or other significant ECG abnormalities.
- •Current or history of Class III or IV heart failure as defined by the NYHA functional classification system
- •Patients with prior anthracycline exposure, previous central thoracic radiation that included heart in radiation port, or a history of NYHA Class II cardiac function.
- •Poorly controlled hypertension
- •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 venous thrombosis or pulmonary embolism in the past 3 months
- •History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
- •Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin
- •Patients with bowel obstruction or any condition that impairs their ability to swallow and retain sunitinib tablets.
- •Use of agents with proarrhythmic potential is not permitted during the study.
- •Must be able to stop prohibited selected CYP3A4 inhibitors/inducers prior to starting sunitinib
- •Patients with pre-existing hypothyroidism prior to enrolment are ineligible unless they are euthyroid on medication.
- •Pregnant or lactating women, positive pregnancy test, women of childbearing potential who do not agree to use adequate contraception prior to study entry and for the duration of study participation.
- •Known HIV-positive patients on combination antiretroviral therapy
- •Greater than +1 proteinuria on urinary dipstick if also >1g urinary protein/24hrs
研究组 & 干预措施
Open label - Sunitinib
Sunitinib, 50mg daily, once daily for 4 weeks followed by a 2-week break
干预措施: Sunitinib (Drug)
结局指标
主要结局
Clinical Benefit Rate (CBR) Which is Defined as Either a Partial Response (PR) Complete Response (CR) or Stable Disease (SD) for ≥ 12 Weeks Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
时间窗: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
The primary endpoint of this study was disease control rate (DCR) defined as a partial response (PR), complete response (CR), or stable disease maintained for ≥12 weeks from the initiation of treatment. Tumour response to sunitinib was assessed as per RECIST 1.1 using CT-imaging. Clinically apparent lesions needed to be \>10mm by calliper measurement to be included as targets. The primary endpoint was met despite closing to accrual early.
次要结局
- Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period(Within 7 days of study registration and every 12 weeks (2 cycles) up to treatment discontinuation (an average of 13.5 6-week cycles or about 1.5 years).)
- Overall Survival(From time of enrollment until loss to follow-up or death (approximately 125 months for longest patient on treatment).)
- Time to Progression(Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).)
- Overall Response Rate (PR) + (CR)(Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).)