A Phase I-II Dose Finding and Early Efficacy Study of Combination Therapy With Erlotinib (Tarceva), Gemcitabine, Bevacizumab (Avastin), and Capecitabine in Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Part A (Phase I): Dose-limiting Toxicity (DLT)
研究概览
简要总结
Pancreatic cancer is an aggressive, largely chemo-resistant disease with a poor prognosis. EGFR and VEGF are both overexpressed in pancreatic cancers and thought to contribute to tumour development and progression. The combination of gemcitabine and capecitabine has recently been shown to be effective in advanced pancreatic cancer. The combination of gemcitabine plus erlotinib has also been shown to be effective in advanced pancreatic cancer. The aim of this study is to assess whether combining a chemotherapy doublet (gemcitabine plus capecitabine) and a biologic doublet (erlotinib plus bevacizumab) is a safe and effective way to treat advanced pancreatic cancer by targeting multiple tumour stimulating mechanisms simultaneously.
详细描述
To establish the safety and efficacy of a combination of four drugs (capecitabine, gemcitabine, erlotinib and bevacizumab) in the treatment of patients with locally advanced or metastatic pancreatic cancer. The study will be divided into two parts:
Part A (Phase I ): Is to establish the optimal dose of capecitabine for combination with gemcitabine, bevacizumab and erlotinib. This part of the study is necessary in order to characterise any increased side effects that may occur as a result of this combination of drugs. The dose of capecitabine will be increased in cohorts containing 3 to 6 patients(according to standard dose escalation study design) whilst side effects are closely monitored. The doses of the other three drugs will remain fixed during this period:
- Gemcitabine: 1000 mg/m2 Days 1, 8, 15
- Bevacizumab: 5 mg/kg every two weeks iv
- Erlotinib: 100 mg/day orally
Maximum tolerated dose is the dose at which 2 out of a cohort of three to six patients experience dose-limiting toxicity within the first cycle (28 days) of treatment. The recommended dose for further evaluation will be one dose level below this.
Part B (Phase II): Once a recommended dose of capecitabine has been chosen, this will be used for the remainder of the trial to further characterise the efficacy and safety of the drug combination in this group of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas
- •Locally advanced or metastatic disease
- •Not amenable to curative resection
- •No invasion of adjacent organs (e.g., duodenum or stomach) by CT scan
- •Unidimensionally measurable disease as assessed by CT in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
- •No evidence of brain metastasis
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Life expectancy:
- •Greater than 3 months
- •Hematopoietic:
- •Granulocyte count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ upper limit of normal
- •Serum albumin > 26 g/litre
- •Creatinine ≤ 180 micromoles/litre OR
- •Creatinine clearance ≥ 50 mL/min
- •Cardiovascular:
- •No clinically significant cardiovascular disease
- •No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg on medication)
- •No arterial thromboembolic event within the past 6 months, including any of the following:
- •Myocardial infarction
- •Unstable angina pectoris
- •Cerebrovascular accident
- •Transient ischemic attack
- •No New York Heart Association grade II-IV congestive heart failure
- •No serious cardiac arrhythmia requiring medication
- •Not pregnant or breast feeding
- •Fertile patients must use effective contraception during study participation
- •No serious or non-healing wound, ulcer, or bone fracture
- •No infection requiring parenteral antibiotics
- •No major bleeding diathesis or coagulopathy
- •No significant traumatic injury within the past 28 days
- •No surgery within the last 28 days or anticipation for the need for major surgery during the course of study treatment
- •No other active malignancy except non-melanoma skin cancer and cervical cancer in-situ
- •No history of known dihydropyrimidine dehydrogenase (DPD) deficiency
- •No lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication
- •PRIOR CONCURRENT THERAPY:
- •No previous chemotherapy, radiotherapy or other investigational drug treatment for metastatic disease (including VEGF or EGFR antagonists)
- •No previous preoperative or adjuvant chemotherapy, radiotherapy or other investigational drug treatment.
- •No full dose anti-coagulation (i.e. warfarin or full dose low molecular weight heparin) prior to starting study treatment.
- •No ongoing treatment with aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
排除标准
- 未提供
结局指标
主要结局
Part A (Phase I): Dose-limiting Toxicity (DLT)
Part B (Phase II): Overall response rate (complete response and partial response)
次要结局
- The secondary efficacy objectives of the trial are: One year survival and median overall survival
- The secondary safety objectives are: Toxicity,Quality of life
- and Assessment of pain
- Progression free survival, Disease control rate.