Randomized Phase II Study of Axitinib in Patients With Recurred or Metastatic Adenoid Cystic Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS) rate
研究概览
简要总结
To understand efficacy of axitinib in recurred or metastatic adenoid cystic carcinoma
详细描述
Adenoid cystic carcinoma (ACC) is a rare variant of adenocarcinoma that occurs in secretory glands such as in salivary glands. Although ACC is histologically low grade and slow-growing, more than half of patients eventually have recurrent and/or metastatic disease.
The natural course of metastatic disease with ACC is relatively indolent; however, most patients with metastatic disease ultimately die from their cancer. The management of recurred / metastatic ACC is a distinct therapeutic challenge because of its insidious local growth pattern, propensity for perineural involvement, tendency for distant metastasis, and pronounced ability to recur over a prolonged period.
- Current treatment
The role of systemic chemotherapy in ACC is very limited and objective response to any cytotoxic or molecular targeted agent is infrequent, and the optimum regimen is unclear. Because of the rarity of ACC, there are few clinical trials investigating the efficacy of systemic chemotherapy. Recurrent/metastatic ACC is an incurable disease with no standard treatments.
VEGF is highly expressed in ACC and its expression correlates with stage, tumor size, vascular invasion, recurrence and metastasis. High expression of VEGF and Ki-67 were independent poor prognostic factors in ACC. MYB/NFIB translocation has recently identified in ACC and MYB protein over expression was found in ACC. MYB over-expression in ACC has been correlated to the increased expression of genes involved in vascular endothelial growth factor (VEGF), KIT . More than 70% of ACCs highly express the oncogenic transcription factor c-myb, which drives expression of genes that activate VEGFR and c-kit pathways.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenoid cystic carcinoma
- •Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI, MIBI scan) or X-ray taken >9 months prior to baseline compared to a previous image. Progression must be documented according to RECIST 1.1 criteria.
- •Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent
- •Presence of at least one measurable target lesion for further evaluation according to RECIST 1.1 criteria
- •18 years or older
- •ECOG performance status 0, 1
- •Adequate organ function
- •ANC ≥ 1500/ μL
- •Platelets ≥100,000/ μL
- •Hemoglobin ≥ 9.0 g/dL
- •Serum creatinine ≤1.5 x ULN
- •Serum bilirubin ≤1.5 x ULN
- •AST, ALT, ≤3.0 x ULN (regardless of liver metastasis)
- •A patient with the willingness to comply with the study protocol during the study period and capable of complying with it
- •A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.
排除标准
- •A patient with no measurable disease
- •Prior chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)
- •A patient with intestinal obstruction or impending obstruction, recent active upper GI bleeding
- •A pregnant or lactating patient
- •A patient of childbearing potential without being tested for pregnancy at baseline or with being tested for positive. (A postmenopausal woman with the amenorrhea period of at least 12 months or longer is considered to have non-childbearing potential)
- •A man or woman of childbearing potential who has no willingness to use a contraceptive measure during the study
- •A patient with history of another malignant disease within past 5 years, except curatively treated basal cell carcinoma of skin, early gastric cancer and cervical carcinoma in situ.
- •A patient with history of uncontrolled seizures, central nervous system disorder or psychiatric disorders that are considered clinically significant by the investigator that would prohibit the understanding of informed consent or that may be considered to interfere with the compliance of the administration of the study medications.
- •A patient with clinically significant heart disease (e.g. congestive heart failure, symptomatic coronary artery diseases, cardiac arrhythmia, etc) or myocardial infarction within past 12 months.
- •A patient with organ transplantation requiring immunosuppressive therapy
研究组 & 干预措施
axitinib
Axitinib 5 mg twice (10mg) daily po medication until progression or development of unacceptable toxicity (4 weeks is considered as one cycle).
干预措施: Axitinib (Drug)
observation
Observation. if disease progression is detected, cross-over will be permitted.
干预措施: Observation (Other)
结局指标
主要结局
Progression-free survival (PFS) rate
时间窗: 6 months
次要结局
- overall survival(1 year)
- duration of response(1 year)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(1 year)
- response rate(1 year)
研究者
Bhumsuk Keam
Clinical Assistant Professor
Seoul National University Hospital