Clinical Study of Apatinib in the Treatment of Platinum Resistant Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Objective remission rate, ORR
研究概览
简要总结
For patients with "Platinum-resistant recurrent ovarian cancer" after second-line chemotherapy failure Using apatinib as a single drug Clinical efficacy observation Single study no control
详细描述
The overall 5-year survival rate of ovarian cancer is 45%. The mortality rate of ovarian cancer accounts for the first in gynecologic cancer deaths. Ovarian cytoreductive surgery and postoperative platinum based chemotherapy are the standard treatment for advanced ovarian cancer. About 80% of ovarian cancer will eventually show relapse and metastasis. All patients with recurrent ovarian cancer will eventually develop into "platinum resistance". Platinum resistance was found in 1-6 months with platinum-free interval. There is no standard treatment protocol for recurrent ovarian cancer of "platinum resistant," usually with platinum-free single chemotherapy, such as: paclitaxel, docetaxel, liposomal doxorubicin, gemcitabine, topotecan and other. The response rate was 10%-30%, the median progression free survival was <4 months, and the median overall survival time was 12 months with platinum-free single-agent chemotherapy. The incidence of grade 3-4 hematologic or non-hematologic toxicity is about 40%. And chemotherapy has 14% mortality rate within 30 days of the start of single-agent chemotherapy in the literature reported. VEGF plays an important role in invasion and metastasis of ovarian cancer. VEGF directly stimulates tumor cell proliferation, growth and migration, and promotes ovarian cancer metastasis. The growth and metastasis of ovarian cancer cells are related to the quantity of VEGF. It has confirmed that inhibition of VEGF function can inhibit angiogenesis and inhibit the growth and metastasis of ovarian cancer cells in vivo experiments. The Chinese State Food and Drug Administration approved small molecular targeting drug, apatinib, for the treatment of advanced gastric cancer, for approval in December 13, 2014. The role of apatinib is the intracellular ATP binding site of VEGFR2 tyrosine receptor, which blocks the signal transduction of VEGF binding and leads to tumor angiogenesis inhibition. Apatinib can inhibit VEGFR2 effectively at a very low concentration, and a higher concentration can inhibit the platelet derived growth factor receptor (PDGFR), c-Kit and c-Src. Apatinib has only 20% grade 3-4 hematological and non hematological toxicity in the treatment of metastatic gastric cancer and gastro-esophageal junction adenocarcinoma. Deng et al reported one cases of progressive ovarian cancer. After 4-line chemotherapy resistance, a daily oral apatinib 500 mg was taken and a longer progression free survival (11.3 months) was obtained. Xie Congying et al of the First Affiliated Hospital of Wenzhou Medical University had a report in the 2017 ESMO conference. The report reviewed 15 cases of recurrent and metastatic ovarian cancer with a single drug atapatinib in the treatment of more than 2 lines of chemotherapeutic drug resistance. The median progression free survival was 5 months, the objective remission rate was 53.3% and the disease control rate was 73.3%. It is known from the above reports that apatinib has good efficacy and low toxicity in the treatment of "platinum resistant" recurrent ovarian cancer, but there is lack of prospective study.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, age ≥18 years, signed informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Patients must have a life expectancy of at least 3 months.
- •Histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary. Failure of at least two-line chemotherapy OR platinum resistant ovarian cancer (defined as relapsing within 6 months after a platinum based chemotherapy) OR platinum refractory ovarian cancer (defined as progressing during a platinum based chemotherapy).
- •Criteria for recurrence or metastasis: blood CA125 is more than 2 times the upper limit of normal value, or imaging findings (CT/MRI/PET-CT) show recurrence or metastasis, or ascites cancer cells are positive.
- •Platinum refractory or resistant criteria: relapse or metastasis within 6 months end of platinum based chemotherapy.
- •The interval time to last chemotherapy was more than 4 weeks.
- •The patient received radiotherapy or surgery for more than 4 weeks, and the wound healed completely.
- •Patients must have adequate organ function as defined by the following criteria: White blood cell count ≥ 3 x 10^9/L, Absolute neutrophil count (ANC) (≥ 1.0 x 10^9/L), Hemoglobin of ≥ 80 g/L, Platelets ≥ 70 x 10^9/L. Total bilirubin ≤ 1 x upper limit of normal (ULN), AST and ALT ≤ 2 x ULN. Serum creatinine ≤ 1 x ULN
- •The main organs (liver, kidney and heart) function are basically normal.
排除标准
- •Had prior exposure to apatinib or has known allegies to apatinib.
- •History of other malignant tumors (except those with cured basal cell carcinoma and cervical carcinoma in situ).
- •History of myocardial infarction, or unstable angina, or New York Heart Association (NYHA) Grade III-IV within 6 months prior to Day
- •Patients with QT interval prolongation.
- •Inadequately controlled hypertension.
- •Serious, non-healing wound, active ulcer, bowel obstruction.
- •History of abdominal fistula or gastrointestinal perforation within 28 days prior to Day
- •Evidence of bleeding diathesis or coagulopathy.
- •Patients with positive urine protein.
- •Major surgical procedure within 28 days prior to Day
- •Symptomatic central nervous system (CNS) metastasis.
研究组 & 干预措施
apatinib
1 times a day, atapinib, 500 mg, is taken orally
干预措施: Apatinib (Drug)
结局指标
主要结局
Objective remission rate, ORR
时间窗: 3 years
Complete remission (CR) + partial remission (PR)
次要结局
- Overall survival(3 years)
- disease control rate, DCR(3 years)
- progression- free survival, PFS(3 years)
- grade 3-4 hematologic or non hematologic toxicity(3 years)