A Randomized, Multicenter, Phase II Trial of Cisplatin, Irinotecan and Bevacizumab (PCA) vs. Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 4
- 主要终点
- 7-month Progression-Free Survival
研究概览
简要总结
There is no clear standard of care for metastatic stomach or esophageal cancer in the United States. The purpose of this research study is to determine the differences between two regimens of chemotherapy; Arm A: PCA (Cisplatin, Irinotecan and Bevacizumab) and Arm B: TPCA (Docetaxel, Cisplatin, Irinotecan and Bevacizumab). Docetaxel, Cisplatin, and Irinotecan are traditional chemotherapy drugs. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body). Bevacizumab is believed to stop the formation of new blood vessels that carry nutrients to tumors. Both of the chemotherapy regimens (PCA and TPCA) have been studied in patients with esophageal and gastric cancer, and we are trying to determine if one regimen will keep your cancer from growing and improve how long you can live.
详细描述
OBJECTIVES:
Primary
* To evaluate progression-free survival at 7 months in metastatic esophageal and gastric patients treated with either PCA or TPCA
Secondary
- To determine overall survival
- To determine the response rate (RECIST) in measurable disease patients
- To evaluate type and severity of toxicities associated with each regimen
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, unresectable esophageal, GE junction or gastric adenocarcinoma (including adenosquamous, or undifferentiated carcinoma). Measurable disease is not required.
- •18 years of age or older
- •ECOG Performance Status=2
- •Life expectancy of 12 weeks or greater
- •Adequate bone marrow, renal and liver function as outlined in the protocol.
- •Men and women of childbearing potential must use adequate contraception
排除标准
- •Prior chemotherapy (except as part of pre- or post-operative therapy, completed at least 1 prior to start of this protocol).
- •Squamous cell carcinoma histology of esophageal, GE junction or gastric tumor
- •Known history of allergy or hypersensitivity to Chinese hamster ovary products, polysorbate 80, or any of the study drugs
- •Treatment or planned participation in an experimental drug study within 4 weeks of C1 D
- •Concurrent use of herbal medications or other alternative therapies
- •Major surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies, within 7 days of cycle 1 day 1
- •Palliative radiation to 25% or less of bone marrow, must be completed > 2 weeks prior to day 1, palliative radiation to > 25% of bone marrow, must be completed > 4 weeks prior to day 1
- •Myocardial infarction, unstable angina, CVA or TIA or other thrombotic event in the past six months
- •Inadequately controlled hypertension (defined as systolic blood pressure of >150mmHg and/or diastolic blood pressure of > 100mmHg). Initiation of antihypertensive medication is recommended, however adequate control of blood pressure must be documented prior to C1 D1
- •No history of prior hypertensive crisis or hypertensive encephalopathy
- •NYHA Grade II or greater congestive heart failure
- •Clinically significant peripheral vascular disease
- •Active bleeding from primary tumor
- •Evidence of bleeding diatheses or coagulopathy (other than deep venous thrombosis, portal vein thrombosis, pulmonary embolism, or atrial fibrillation). Patients on therapeutic anticoagulation may be enrolled provided they have been clinically stable on anticoagulation for a least 2 weeks prior to C1 D
- •Uncontrolled serious medical or psychiatric illness
- •Uncontrolled diarrhea
- •Peripheral neuropathy
- •No known brain or other CNS metastasis by history or clinical examination
- •Other active malignancy other than non-melanoma skin cancer or in-situ cervical carcinoma. A resected or previously treated cancer (other than in-situ carcinoma) must have demonstrated no evidence of recurrence for at least 3 years
- •Urine protein:creatinine ratio 1.0 or greater at screening
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess with 6 months of C1 D1
- •Serious, non-healing wound, ulcer or bone fracture
- •Pregnant or breast feeding
- •Inability to comply with study and/or follow-up procedures
- •History of HIV seropositivity, hepatitis C virus, acute or chronic hepatitis B, or other serious chronic infection
研究组 & 干预措施
Arm A: PCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally, on days 1 and 8 of each cycle, patients received cisplatin 30 mg/m2 IV over 30 minutes and then irinotecan 65 mg/m2 IV over 30 minutes of each 3-week cycle. Treatment could continue until disease progression or unacceptable toxicity.
干预措施: Bevacizumab (Drug)
Arm A: PCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally, on days 1 and 8 of each cycle, patients received cisplatin 30 mg/m2 IV over 30 minutes and then irinotecan 65 mg/m2 IV over 30 minutes of each 3-week cycle. Treatment could continue until disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm A: PCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally, on days 1 and 8 of each cycle, patients received cisplatin 30 mg/m2 IV over 30 minutes and then irinotecan 65 mg/m2 IV over 30 minutes of each 3-week cycle. Treatment could continue until disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
Arm B: TPCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally on days 1 and 8 of each cycle, patients received docetaxel 30 mg/m2 IV over 30 minutes followed by cisplatin 25 mg/m2 IV over 30 minutes and then irinotecan 50 mg/m2 IV over 30 minutes of each 3-week cycle.
干预措施: Cisplatin (Drug)
Arm B: TPCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally on days 1 and 8 of each cycle, patients received docetaxel 30 mg/m2 IV over 30 minutes followed by cisplatin 25 mg/m2 IV over 30 minutes and then irinotecan 50 mg/m2 IV over 30 minutes of each 3-week cycle.
干预措施: Irinotecan (Drug)
Arm B: TPCA
Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally on days 1 and 8 of each cycle, patients received docetaxel 30 mg/m2 IV over 30 minutes followed by cisplatin 25 mg/m2 IV over 30 minutes and then irinotecan 50 mg/m2 IV over 30 minutes of each 3-week cycle.
干预措施: Docetaxel (Device)
结局指标
主要结局
7-month Progression-Free Survival
时间窗: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Relevant for this endpoint was disease status at 7 months of follow-up.
7-month progression-free survival is the probability of patients remaining alive and progression-free at 7-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
次要结局
- Overall Survival(Patients in the study cohort were followed up to approximately 2.5 years as of this analysis.)
- Best Response(Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis..)
- Overall Response (OR) Rate(Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis.)
- Progression-Free Survival(Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Patients were followed for up to 2.5 years as of this analysis.)
研究者
Peter C. Enzinger, MD
Principal Investigator
Dana-Farber Cancer Institute