A Randomized Phase II Study of Gemcitabine/Cisplatin With or Without Sorafenib to Evaluate the Efficacy and Safety in Patients With Locally Advanced or Metastatic Pancreatic Cancer. MAPS Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 114
- 试验地点
- 17
- 主要终点
- Progression Free Survival
研究概览
简要总结
This is multicentre, open-label, randomized, phase II trial in patients with locally advanced or metastatic pancreatic cancer. Subjects will be randomized in a 1:1 ratio to receive gemcitabine/cisplatin in combination with Sorafenib (arm A) or gemcitabine/cisplatin alone (arm B), as first-line chemotherapy.
详细描述
Up to date no standard treatment is available for pancreatic cancer. Although gemcitabine is commonly used in patients with pancreatic cancer with the purpose of symptom palliation, there is no clear evidence of efficacy in terms of survival increase or progression control. Furthermore, attempts at improving results by combining gemcitabine with other cytotoxic drugs failed to obtain any advantage. Recently, an EGFR inhibitor (erlotinib) showed a small survival advantage when combined with gemcitabine. results obtained with a combination of gemcitabine and oxaliplatin seem more promising. A meta-analysis of randomised trials comparing gemcitabine versus gemcitabine and platinum analogues showed a statistical significant survival advantage for the combination.
Sorafenib is an inhibitor of the RAS/RAF signalling pathway. Furthermore, sorafenib is able to inhibit both VEGFR and PDGFR.
Since RAS and RAF mutations are quite common in pancreatic cancer, Sorafenib could be useful in the management of these tumours. Furthermore, it may be combined with gemcitabine and cisplatin without any pharmacokinetic interaction or enhanced toxicity.
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
- None
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
- •Signed written informed consent prior to beginning protocol specific procedures
- •Male or female 18 to 75 years of age
- •Diagnosis of histologically confirmed adenocarcinoma of the pancreas
- •Locally advanced (non-resectable) or metastatic pancreatic cancer
- •Presence of at least one uni-dimensional indicator lesion measurable by CT scan or MRI in not an irradiated area (RECIST criteria)
- •Karnofsky performance status of ≥ 70 at study entry
- •Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL
- •Bilirubin level either normal or < 1.5 x ULN
- •ASAT and ALAT ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present)
- •Serum creatinine < 1.5 x ULN
- •Amylase and lipase ≤ 1.5 x the upper limit of normal
- •PT or INR and PTT < 1.5 x upper limit of normal (subjects who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate provided that no evidence of underlying abnormality in these parameters exists).
- •Effective contraception for both male and female patients if the risk of conception exists
排除标准
- •Brain metastases
- •Previous chemotherapy for locally advanced or metastatic pancreatic cancer.
- •Adjuvant therapy if documented recurrence is within 6 months after the end of adjuvant treatment)
- •Radiotherapy within 4 weeks prior to study entry
- •Major surgery within 4 weeks of first dose of study drug
- •Concurrent chronic systemic immune therapy
- •Any investigational agent(s) 4 weeks prior to entry
- •Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months
- •Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
- •Acute or subacute intestinal occlusion or history of inflammatory bowel disease
- •Known grade 3 or 4 allergic reaction to any of the components of the treatment
- •Known drug abuse/ alcohol abuse
- •Legal incapacity or limited legal capacity
- •Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
- •Women who are pregnant or breastfeeding
- •Acute or subacute intestinal occlusion
- •Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial).
研究组 & 干预措施
A
Sorafenib 400 mg po bid, continuously
Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days.
干预措施: Sorafenib 400 mg po bid, continuously (Drug)
B
Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days
干预措施: Gemcitabina, Cisplatino (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: time from randomization date to date of local or regional relapse
次要结局
- - overall Response Rate (RECIST Criteria) - duration of response - overall survival time(time from the day of randomization to the date of death from any cause)