NCT01189227终止3 期
A Phase III Study Evaluating the Role of Perioperative Chemotherapy in Patients With Potentially Resectable Hepatic Colorectal Metastases
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 283
- 主要终点
- Recurrence-free Survival (RFS)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to kill tumor cells or stop them from growing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether giving combination chemotherapy before and after surgery is more effective than giving combination chemotherapy after surgery.
PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before and after surgery to see how well it works compared to giving combination chemotherapy after surgery in treating patients with colorectal cancer with liver metastases that could be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To evaluate the difference in recurrence-free survival (RFS) of patients with potentially resectable hepatic colorectal metastases receiving perioperative (preoperative plus postoperative) adjuvant chemotherapy vs only postoperative adjuvant chemotherapy following liver resection for colorectal metastases.
Secondary
- To compare the proportion of patients between study arms who are R0 or R1 resected, alive, and free of recurrence at 6 months.
- To compare RFS between study arms in the cohort of patients event-free at 6 months.
- To compare overall survival between study arms.
- To evaluate the difference in R0 and combined R0 + R1 resection rates in patients receiving neoadjuvant therapy and those undergoing initial surgical resection.
- To compare the postoperative morbidity profile between study arms.
- To evaluate the safety and toxicity profile of postoperative and perioperative administration of chemotherapy and bevacizumab.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed colorectal adenocarcinoma
- •Hepatic metastasis (no histologic confirmation required) and no evidence of extrahepatic metastatic disease within the past 4 weeks by one of the following imaging studies*:
- •PET/CT scan with contrast
- •PET scan AND CT scan with contrast
- •PET scan AND MRI with contrast
- •PET/CT scan without contrast AND MRI with contrast NOTE: *If findings noted in imaging study reports are equivocal, the determination of whether or not the findings represent extrahepatic disease will be at the investigator's discretion.
- •No history of or concurrent evidence of extrahepatic metastases
- •Patients with regional nodes that are suspicious on imaging and are associated with the primary colorectal tumor are eligible provided the nodes will be resected with the primary tumor after randomization
- •No radiographic evidence of metastases to portal lymph nodes (node > 1 cm in diameter) unless the node(s) are proven by biopsy to be negative
- •No anal, small bowel, or appendiceal carcinoma
- •No sarcoma, lymphoma, or carcinoid colorectal malignant diseases
- •Within 4 weeks before randomization, the liver metastases must be determined by a hepatic surgeon to be resectable based on meeting both of the following criteria:
- •A complete resection can be performed in a single operation
- •There are ≥ 2 uninvolved contiguous segments of the liver
- •Meets one of the following criteria:
- •Primary tumor and regional nodes resected with clear surgical margins and no evidence of extrahepatic disease
- •Unresected primary tumor with plans to resect the primary tumor before randomization
- •Unresected primary tumor with plans to resect the primary tumor and the liver metastases in a single surgical procedure performed after randomization
- •No unresected primary tumor in the colon or rectum with significant symptoms related to obstruction or that will require radiotherapy
- •PATIENT CHARACTERISTICS:
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Life expectancy ≥ 5 years (excluding the diagnosis of metastatic CRC)
- •absolute neutrophil count (ANC) ≥ 1,200/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Total bilirubin ≤ upper limit of normal (ULN)
- •aspartate aminotransferase (AST) ≤ 5.0 times ULN
- •Alkaline phosphatase ≤ 5.0 times ULN
- •Serum creatinine ≤ ULN OR calculated creatinine clearance ≥ 30 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 180 days after completion of study treatment
- •Considered a potential candidate for a major hepatic surgical procedure
- •No grade 3 or 4 anorexia, grade 3 nausea, or vomiting ≥ grade 2 (per CTCAE v4.0) related to metastatic disease
- •No paresthesias, peripheral sensory neuropathy, or peripheral motor neuropathy ≥ grade 2 per Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 (patients with grade 2 neuropathy who will receive FOLFIRI are eligible)
- •No uncontrolled high BP defined as systolic BP ≥ 160 mm Hg OR diastolic BP ≥ 100 mm Hg, with or without antihypertensive medication (patients with initial BP elevations are eligible provided initiation or adjustment of BP medication lowers pressure to meet this criteria)
- •Documented history of congestive heart failure requiring chronic medical therapy
- •No active inflammatory bowel disease
- •No active infection or chronic infection requiring chronic suppressive antibiotics
- •No known bleeding diathesis or coagulopathy
- •No symptomatic interstitial pneumonitis OR definitive evidence of interstitial pneumonitis described on CT scan, MRI, or chest x-ray in asymptomatic patients
- •No other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 1 year ago
- •Patients with carcinoma in situ of the cervix, CRC in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin diagnosed and treated at any time before study treatment are eligible
- •No known Gilbert syndrome
- •Not known to be homozygous for the UGT1A1 allele (for patients who will receive FOLFIRI chemotherapy)
- •No prior serious hypersensitivity reaction to any of the agents administered as part of study treatment (determination of "serious" is at the investigator's discretion)
- •No other serious concurrent medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study, or cause a delay in the initiation of therapy (surgery or chemotherapy) longer than 4 weeks following randomization
- •No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
- •No pre-existing chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that, in the opinion of the investigator and hepatic surgeon, would limit the patient's ability to undergo hepatic metastasectomy
- 另有 9 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm 1: Postoperative chemotherapy
Experimental
Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.
干预措施: Postoperative chemotherapy (Procedure)
Arm 2: Perioperative chemotherapy
Experimental
Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.
干预措施: Perioperative chemotherapy (Procedure)
结局指标
主要结局
Recurrence-free Survival (RFS)
时间窗: From study entry until the date of recurrence or death or for a maximum of 5 years.
Time to recurrence or death
次要结局
- RFS of Patients Event-free(From study entry until the date of recurrence or for a maximum of 6 months.)
- Overall Survival(From study entry until the time of death or for a maximum of 5 years.)
- The Difference in R0 and Combined R0 + R1 Resection Rates Between the Two Arms.(Assessed at the time of surgery)
- Frequencies of Selected Postoperative Surgical Complications and Other Adverse Events Within 30 Days of Surgery(Assessed within 30 days from the time of surgery)
- Frequencies of Adverse Events as Assessed by the NCI CTCAE v4.0(From study entry through 3 months after the last treatment dose.)
研究者
研究点 (283)
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