Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases - A Randomized Phase II/III Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- 18-month hepatic RFS rate
研究概览
简要总结
Currently, no adjuvant study with hepatic arterial infusion in the adjuvant setting is opened. Recently, the results of a phase II study (NCT00268463, NSABP-C-09) assessing the potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR, after resection of CRLM have been reported.
The primary end point was 2-year survival. Fifty-five of 76 eligible patients were able to initiate protocol-directed therapy and completed median of six cycles (range, one to six). Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable patients were alive at 2 years. With a median followup of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7 months. In conclusion alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and were clinically tolerable.
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 metastatic colorectal adenocarcinoma,
- •Curative-intent resection (or ablation) R0 of at least 4 CRLM,
- •Preoperative oxaliplatin- and/or irinotecan-based chemotherapy (successively or concomitantly) +/- non experimental biological therapy, e.g., anti-EGFR or antiangiogenic antibody,
- •Confirmed radiological tumor control before surgery (i.e., objective response or stable disease according to RECIST1.1 criteria),
- •WHO performance status of 0 or 1,
- •Age ≥ 18 years,
- •Adequate hematological function: absolute neutrophil count (ANC) > 2 x 109/L; platelets > 100 x 10^^9/L, hemoglobin (Hb) > 9 g/dL.
- •Adequate liver function: serum bilirubin </= 1.5 x ULN;
- •Aminotransferases levels </= 2.5 ULN (</= 5 ULN if liver metastases in place), and alkaline phosphatase level ≤ 5 ULN
- •Creatinin clearance ≥ 30 ml/min
- •Informed consent signed by the patient or his/her legal representative.
- •Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment.
排除标准
- •Extrahepatic metastatic disease (except ≤3 lung nodules (≤10 mm on chest CT scan) deemed amenable to curative-intent resection/ablation),
- •Symptomatic primary tumor requiring urgent surgery, asymptomatic primary colorectal tumor is not a non-inclusion criteria if its
- •Contraindication to fluoropyrimidines or oxaliplatin, as mentioned in the SMPC of investigational medicinal products
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency
- •Disease progression during, or early hepatic relapse (< 6 months) after the end of, oxaliplatin-based adjuvant chemotherapy following primary tumor resection
- •History of hepatic arterial infusion with any treatment (chemotherapy, radioembolisation),
- •Peripheral neuropathy> grade 1,
- •History of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix
- •Concomitant administration of cimetidine
- •Concomitant medications/comorbidities that may prevent the patient from receiving study treatments,
- •Patient already included in another clinical trial with an experimental molecule,
- •Pregnancy or lactation,
- •Patients deprived of liberty or under guardianship,
- •Patients unable to undergo medical monitoring test for geographical, social or psychological reasons.
- •Patients must not have any uncontrolled concurrent illness including, but not limited to, severe active or uncontrolled infection, symptomatic congestive heart failure, unstable, angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements resection is planned (REVERSE strategy authorized)
研究组 & 干预措施
Adjuvant HAI oxaliplatin and systemic LV5FU2
started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, and performed every 14 days:
- Oxaliplatin 85 mg/m² in 4-6 hours HAI day (D)1,
- Acide Folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg / m² IV in 46 hours. In both arms, continuation of targeted therapy (if any) used in the preoperative treatment is allowed.
干预措施: Oxaliplatin HAI (Drug)
Adjuvant systemic chemotherapy with mFOLFOX6
started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, every 14 days:
- Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,
- Acide folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg/m² IV in 46 hours.
干预措施: Oxaliplatin IV (Drug)
Adjuvant systemic chemotherapy with mFOLFOX6
started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, every 14 days:
- Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,
- Acide folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg/m² IV in 46 hours.
干预措施: mFOLFOX6 (Drug)
Adjuvant HAI oxaliplatin and systemic LV5FU2
started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, and performed every 14 days:
- Oxaliplatin 85 mg/m² in 4-6 hours HAI day (D)1,
- Acide Folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg / m² IV in 46 hours. In both arms, continuation of targeted therapy (if any) used in the preoperative treatment is allowed.
干预措施: LV5FU2 (Drug)
结局指标
主要结局
18-month hepatic RFS rate
时间窗: Assessed 18 months after inclusion
3-year RFS rate
时间窗: Assessed 3 years after inclusion
次要结局
未报告次要终点