Phase II Trial of Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in best overall response rate
研究概览
简要总结
The majority of endometrial cancer patients with disease spread beyond the uterus will progress within 1 year. Platinum-based chemotherapy was used as the first-line treatment in metastatic or advanced endometrial cancer. There is no standard protocol for the second-line option when tumors persist or recur. In vitro and in vivo studies showed Crizotinib, an approved drug for the treatment of ALK-positive non-small cell lung cancer, demonstrated activities in endometrial cancer with c-MET kinase and Sema domain mutations. As a consequence, a phase 2 clinical trial to investigate the efficacy of Crizotinib in endometrial cancer patients with MET mutation is initiated.
详细描述
In this phase 2 study, the target population is patients with recurrent or persistent metastatic endometrial cancer. The mutation status of c-MET gene will be tested and only patients with c-MET mutation will be enrolled. After enrollment, Crizotinib 250 mg bid will be used orally. CT scan or MRI will be used to determine the response. Crizotinib will be continued till disease progression. Primary end is objective response rate. The secondary endpoints include progression-free survival, overall survival and safety profiles.
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age no less than 20 years and no more than 75 years, at the time of acquisition of informed consent.
- •Histological confirmed epithelial endometrial cancer
- •Disease recurrent after curative therapy or adjuvant therapy including surgery, chemotherapy, radiotherapy or hormone therapy
- •Metastatic/recurrent/persistent endometrial cancer
- •Tumor tissue with high expression in immunohistochemistry stain (IHC) or somatic c-MET mutation
- •Patients with symptomatic recurrent lesion or Image diagnosis (including ultrasound, Computed Tomography or Magnetic Resonance Imaging) recurrent status
- •ECOG Performance status 0-2
- •At least one distinct tumor, not previous irradiated, measurable lesion according to RECIST (version 1.1)
- •Adequate organ function
- •Bone marrow:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L WBC ≥ 3.0 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9 g/dL
- •Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL Renal: Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min (CCr is estimated by Cockcroft-Gault formula)
- •Negative pregnancy test for women of childbearing potential only
- •Patient willing to provide blood sample for research purposes
- •Written informed consent
排除标准
- •Presence or history of malignancy disease other than endometrial cancer that has been diagnosed with past five years
- •Other anti-tumor agent such as systemic chemotherapy, hormone therapy or surgery within 2 weeks before the commencement of study treatment or radiotherapy within 4 weeks before the commencement of study
- •Active uncontrolled infection
- •Significant medical diseases, such as unstable angina, acute or recent myocardial infarction (<6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, ore cent CVA (<6 months before enrollment)
- •Poor compliance
- •Pregnant or breastfeeding women, where pregnancy is confirmed by a positive hCG laboratory test.
研究组 & 干预措施
Crizotinib arm
Crizotinib 250 mg bid orally
干预措施: Crizotinib 250 MG (Drug)
结局指标
主要结局
Change in best overall response rate
时间窗: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks
CT scan or MRI will be used to evaluate the response every 2 cycles according to the RECIST 1.1 criteria. The best overall response rate is the proportion of patients in whom a complete response (CR) or partial response (PR) was observed.
次要结局
- Overall survival(Overall survival will be followed from the start of treatment to death from any cause, up to 104 weeks)
- Progression-free survival(CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks)