NCT02581215已完成2 期
Phase II Randomized, Double-Blind Study of mFOLFIRINOX Plus Ramucirumab Versus mFOLFIRINOX Plus Placebo in Advanced Pancreatic Cancer Patients: Hoosier Cancer Research Network GI14-198
Walid Shaib, MD8 个研究点 分布在 1 个国家目标入组 84 人开始时间: 2016年9月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 8
- 主要终点
- Progression Free Survival (PFS) at 9 Month
研究概览
简要总结
This is a phase II, multicenter, double-blinded, randomized, 2-arm trial evaluating the efficacy and safety of mFOLFIRINOX plus ramucirumab (Arm A) vs. mFOLFIRINOX plus placebo (Arm B) in 94 subjects with advanced pancreatic cancer, not amenable to curative treatment. Both arms will continue treatment until disease progression or unacceptable toxicity.
详细描述
OUTLINE: This is a multi-center study.
EXPERIMENTAL ARM A:
- Oxaliplatin 85 mg/m^2 over 2-4 hours
- Irinotecan 165 mg/m^2 over 90 minutes
- 5-FU 2,400 mg/m^2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm A will receive ramucirumab (RAM) administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.
CONTROL ARM B :
- Oxaliplatin 85 mg/m2 over 2-4 hours
- Irinotecan 165 mg/m2 over 90 minutes
- 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were RAM.
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)
盲法说明
Site pharmacy staff will be unblinded to the study treatment. Subjects, site investigators, site analysis teams, and other site personnel will be blinded to the study treatment.
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
- •Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. .
- •Age ≥ 18 years at the time of consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 7 days prior to registration.
- •Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PCA) who present for first line chemotherapy treatment.
- •No prior first line systemic treatment (prior adjuvant or neoadjuvant treatment is permitted). Subjects whose disease has progressed after 6 months of last systemic chemotherapy or chemo-radiation in the adjuvant or neoadjuvant setting are eligible.
- •Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI).
- •Urine protein < 1+ on dipstick test or routine urinalysis. If the proteinuria on these tests is ≥2+, then a 24-hour urine test must be collected and must demonstrate < 1g proteins in 24 hours to allow participation.
- •Estimated life expectancy of >12 weeks, as assessed by the site investigator.
- •If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) due to unknown risk of teratogenicity of ramucirumab
排除标准
- •Subjects with histology other than adenocarcinoma; Examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas.
- •Ongoing or active infection.
- •Symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia. Symptomatic heart failure per New York Heart Association (NYHA) Class II-IV.
- •Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
- •Acute or sub-acute intestinal obstruction.
- •Interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the site investigator could compromise the subject or the study.
- •Pleural effusion or ascites that causes > grade 1 dyspnea.
- •Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
- •Grade 3 or higher bleeding event ≤ 3 months prior to randomization.
- •Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤ 6 months prior to randomization.
- •History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization.
- •Documented and/or symptomatic or known brain or leptomeningeal metastases.
- •GI perforation/fistula
- •Documented and/or symptomatic or known brain or leptomeningeal metastases.
- •Severely immune-compromised (other than being on steroids), including known HIV infection.
- •Concurrent active malignancy other than adequately treated non-melanoma skin cancer, other noninvasive carcinoma, or in situ neoplasm. A subject with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years.
- •Breast-feeding or pregnant.
- •Prior autologous or allogeneic organ or tissue transplantation.
- •Known allergy to any of the treatment components.
- •Major surgery within 28 days prior to the first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 2 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
- •Any condition that does not permit compliance with the study schedule including psychological, geographical or medical.
- •Receiving medications that can effect clotting ability: warfarin, aspirin (once-daily aspirin use- maximum dose 325 mg/day is permitted), nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. .
- •Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
研究组 & 干预措施
Arm A: Experimental Arm
Experimental
mFOLFIRINOX will be administered every 2 weeks, and consist of:
- Oxaliplatin 85 mg/m2 over 2-4 hours
- Irinotecan 165 mg/m2 over 90 minutes
- 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm A will receive ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.
干预措施: mFOLFIRINOX (Drug)
Arm A: Experimental Arm
Experimental
mFOLFIRINOX will be administered every 2 weeks, and consist of:
- Oxaliplatin 85 mg/m2 over 2-4 hours
- Irinotecan 165 mg/m2 over 90 minutes
- 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm A will receive ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.
干预措施: Ramucirumab (Drug)
Arm B: Placebo Arm
Placebo Comparator
mFOLFIRINOX will be administered every 2 weeks, and consist of:
- Oxaliplatin 85 mg/m2 over 2-4 hours
- Irinotecan 165 mg/m2 over 90 minutes
- 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were ramucirumab
干预措施: mFOLFIRINOX (Drug)
Arm B: Placebo Arm
Placebo Comparator
mFOLFIRINOX will be administered every 2 weeks, and consist of:
- Oxaliplatin 85 mg/m2 over 2-4 hours
- Irinotecan 165 mg/m2 over 90 minutes
- 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
- Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were ramucirumab
干预措施: Placebo (Other)
结局指标
主要结局
Progression Free Survival (PFS) at 9 Month
时间窗: 9 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time of registration until disease progression met by RECIST 1.1 or death from any cause.
次要结局
- Overall Survival (OS)(Up to a maximum of 53 months)
- Response Rate (RR)(Up to 44 months)
- Number of Participants With Adverse Events(From date of first dose until 30 days after the last treatment, assessed up to 44 months)
研究者
Walid Shaib, MD
Sponsor-Investigator
Hoosier Cancer Research Network
研究点 (8)
Loading locations...
相似试验
Unknown
2 期
MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced DiseasePancreatic CancerNCT04089150Australasian Gastro-Intestinal Trials Group120
招募中
2 期
Trial Evaluating Modified FOLFIRINOX and Modified FOLFOX in the Treatment of Locally Advanced or Metastatic Small Bowel AdenocarcinomaLocally Advanced or Metastatic Small Bowel AdenocarcinomaNCT06278545Centre Hospitalier Universitaire Dijon130
已完成
2 期
Study to Assess the Efficacy and Safety of Treatment With FOLFIRI-aflibercept Compared to Initial Treatment With FOLFIRI-aflibercept (for 6 Cycles) Followed by Maintenance With 5FU-aflibercept, in an Elderly Population With mCRC After Failure of an Oxaliplatin-based RegimenMetastatic Colorectal CancerNCT03279289Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)170
Unknown
2 期
Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line TreatmentMetastatic Colorectal CancerNCT02624726Hellenic Oncology Research Group31
已完成
2 期
FOLFOX/Bevacizumab With Onartuzumab (MetMAb) Versus Placebo as First-Line Treatment in Patients With Metastatic Colorectal CancerColorectal CancerNCT01418222Genentech, Inc.194