A Phase 2 Study of Aflibercept and Chemotherapy as First Line Treatment for Metastatic Colorectal Cancer Assessable With DCE-US.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 8
- 主要终点
- Progression-Free Rate will be assessed according to RECIST 1.1 with central radiological review.
研究概览
简要总结
The PULSAR trial is an international, investigator-initiated, single arm open-label phase II study. The aim of this study is to measure the clinical activity of the combination FOLFIRI-aflibercept in an homogeneous group of patients with metastatic colorectal cancer, and treated with a FOLFIRI-aflibercept regimen as first line treatment.
详细描述
Patients with an unresectable metastatic colorectal carcinoma (mCRC) histologically proven will be treated with a combination of Irinotecan/bolus-infusion-5-Fluorouracil/Leucovorin (FOLFIRI regimen) and aflibercept. On day 1 of each cycle patients will receive aflibercept followed by irinotecan, 5-Fluorouracil (FU) and leucovorin (FOLFIRI regimen). This treatment will be repeated every 2 weeks until RECIST progression or unacceptable toxicities, investigator's decision or patient's refusal of further treatment or death, whichever comes first.
All patients will be assessed during their FOLFIRI-aflibercept with Dynamic Contrast Enhanced Ultrasound (DCE-US) at baseline, D7 (± 1 day), D28 (± 2 days).
The recruitment period is 24 months. The average duration of the study per patient will be approximately 12 months, i.e. 3 weeks for screening, 10 months for the combination of FOLFIRI plus aflibercept and 30 days for follow-up of adverse events after the last dose of study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Signed and dated informed consent, and willing and able to comply with protocol requirements
- •Histologically proven adenocarcinoma of the colon and/or rectum
- •Metastatic disease confirmed clinically/radiologically, and evaluable by dynamic contrast ultrasound
- •No prior therapy for metastatic disease
- •Duly documented inoperable metastatic disease, i.e. not suitable for complete curative surgical resection
- •At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
- •Adequate hematological status: neutrophils (ANC) ≥ 1.5 x109/L; platelets ≥ 100x109/L; haemoglobin ≥ 9g/ dL
- •Adequate renal function: serum creatinine level < 1.5 mg/dl and Glomerular Filtration Rate > 50 ml/min by cockroft/ Gault formula
- •Adequate liver function: serum bilirubin ≤ 1.5 x upper normal limit (ULN), alkaline phosphatase, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 5 x ULN
- •Proteinuria < 2+ (dipstick urinalysis) or ≤ 1g/24 hour
- •Female patients must commit to using reliable and appropriate methods of contraception until at least 6 months after the end of Aflibercept and 3 months after the end of Irinotecan (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method until at least 6 months after the end of Aflibercept and 3 months after the end of Irinotecan.
排除标准
- •Uncontrolled hypercalcemia
- •Uncontrolled systemic hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg despite medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy
- •Right-left shunt or severe pulmonary arterial hypertension (pulmonary artery pressure > 90 mmHg)
- •Respiratory distress syndrome
- •Concomitant antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
- •Treatment with any other investigational medicinal product within 28 days prior to study entry
- •History or presence of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizures not controlled with standard medical therapy)
- •Gilbert's syndrome
- •Intolerance to atropine sulfate or loperamide
- •Known dihydropyrimidine dehydrogenase deficiency
- •Treatment with Cytochrome P450 3A4 (CYP3A4) inducers unless discontinued > 7 days prior to registration
- •Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or chronic inflammatory bowel disease, or diverticulitis
- •Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for > 5 years,
- •Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
- •Pregnant or breastfeeding women
- •Patients with known allergy to any excipients to study drugs (including hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue)
- •History of myocardial infarction and/or stroke or other arterial thrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration
- •Poorly controlled cardiac arrhythmias
- •Typical Angina Pectoris at rest within the previous 7 days, or significant worsening of cardiac symptoms in the previous 7 days, or recent intervention on the coronary arteries or other factors suggesting clinical instability (eg recent deterioration of ECG changes in clinical parameters or biological), or acute heart failure, or heart failure stage III or IV, or severe arrhythmias
- •Bowel obstruction
- •History of severe tumour bleeding or bleeding disorders
- •Poorly controlled anti-coagulation therapy (INR > 3.0 on coumadin or heparin compounds)
- •Palliative radiation therapy within 4 weeks prior to registration
- •St John's Wort medication
研究组 & 干预措施
Aflibercept-FOLFIRI
On day 1 of each cycle patients will receive aflibercept followed by irinotecan, 5-FU and leucovorin (FOLFIRI regimen). This treatment will be repeated every 2 weeks until RECIST progression or intolerance.
干预措施: Aflibercept-FOLFIRI (Drug)
结局指标
主要结局
Progression-Free Rate will be assessed according to RECIST 1.1 with central radiological review.
时间窗: At 10-month
次要结局
- Progression-free survival (PFS)(through study completion, an average of 3 years)
- Patterns of PFS according to DCE-US early assessment(at day 28 ± 2)
- Safety and tolerance(up to 30 days after the end of the study treatment)
- Best Response Rate (BRR)(through the end of study treatment, an average of 1 year)
- Progression-free survival rate(through study completion, an average of 3 years)
- Overall Response Rate (ORR) will be determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.(through the end of study treatment, an average of 1 year)
- Pharmacodynamic activity(at day 7 ± 1, and day 28 ± 2)