A Prospective, Randomized, Controlled, Double-blind, Multi-center Clinical Study of Nimotuzumab Combinated With Gemcitabine Contrast to Placebo Combinated With Gemcitabine in K-RAS Wild-type,Locally Advanced and Metastatic Pancreatic Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 25
- 主要终点
- Overall Survival（OS）
研究概览
简要总结
Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer
详细描述
Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer.Secondary objectives include time to progression（TTP）,progression-free survival（PFS）,Objective Response Rate（ORR）,Disease Control Rate（DCR）,Clinical Benefit Response（CBR）and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age:18-75 years old
- •Histological or cytological diagnosis that are unsuitable for radical radiotherapy or surgical treatment of locally advanced or metastatic pancreatic adenocarcinoma (≥6 months to the last adjuvant chemotherapy)
- •Has at least one objective measurable lesion can be evaluated according to Response Evaluation Criteria in Solid Tumors1.1(Helical CT examination of the longest diameter of target lesions≥10mm, such as lymph node metastasis only need the shortest path ≥15mm)
- •Life expectancy ≥12 weeks
- •K-RAS tumor tissue detected as the wild-type
- •Aspartate transaminase（AST）/aminotransferase（ALT）≤2.5×ULN，AST /ALT≤5×ULN（if liver metastases）；Total bilirubin≤2×ULN，Total bilirubin≤3×ULN（if liver metastases）；Absolute neutrophil count≥1.5×109/L；Blood platelet≥100×109/L；Hemoglobin≥90 g/L；Creatinine clearance≥60ml/min
- •Volunteered to participate this study, written informed consent and has a good compliance
- •Patients of childbearing age and their spouses are willing to take contraceptive measures
排除标准
- •Before this study had received the following treatments：As a means of anti-tumor palliative chemotherapy and molecular targeted therapy.Target lesion had received radiotherapy without progression.within 4 weeks or be participating in clinical trials of other therapeutic/ interventionist clinical trial.
- •Undergone major surgery within 4 weeks.
- •The brain metastasis or leptomeningeal metastasis.
- •Has a history of malignancy other than the pancreatic cancer (except for the cured cervix in situ or basal cell carcinoma, and a five-year cure other cancers).
- •The merger has symptoms of ascites and requires clinical treatment. Accompanied by other serious disease, including but not limited:Congestive heart failure which is difficult to control (NYHA III or IV), Unstable angina, Poorly controlled arrhythmia, Uncontrolled moderate to severe hypertension(systolic blood pressure（SBP）>160 mm Hg or diastolic blood pressure（DBP）>100 mm Hg).Active infection.Diabetes which is difficult to control.Has mental illness which impacts the informed consent and / or compliance program.HIV infection.There is serious illness that other researchers consider is unsuitable to participate this study.
- •Known allergy to anti-EGFR antibody formulations.
研究组 & 干预措施
Nimotuzumab and Gemcitabine
nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.
Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.
干预措施: nimotuzumab (Drug)
Nimotuzumab and Gemcitabine
nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.
Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.
干预措施: Gemcitabine (Drug)
Placebo and Gemcitabine
placebo,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.
Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.
干预措施: Gemcitabine (Drug)
Placebo and Gemcitabine
placebo,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.
Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.
干预措施: Placebo (Other)
结局指标
主要结局
Overall Survival（OS）
时间窗: up to 3 years
The primary endpoint was overall survival (OS, defined as from randomization to death due to any cause). We screened 90 pts (90 patients were allocated for treatment) from 480 pts, of whom 8 pts were excluded due to serious violation of the inclusion criteria: 7 pts with K-Ras mutants, 1 pt with gallbladder cancer. Finally, 82 pts were included in FAS. The primary end point was evaluated in the full analysis set (FAS; all eligible patients who received at least one dose of nimotuzumab/placebo and had one evaluation of efficacy).
次要结局
- Time to Progression（TTP）(up to 3 years)
- Progression Free Survival（PFS）(up to 3 years)
- Clinical Benefit Response（CBR）(every 8 weeks, up to 5.4 months)
- Objective Response Rate（ORR）(Once every eight weeks，up to 5.4 months)
- Number of Participants With Adverse Events(up to 75.2 months)
- Disease Control Rate（DCR）(Once every eight weeks，up to 5.4 months)