Multimodality Treatment Including Pre- and Postoperative Systemic Chemotherapy Plus Cetuximab, Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Peritoneal Carcinomatosis Arising From Wild Type K-ras Colon Cancer: A Prospective Multicenter Phase II Study.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 7
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
The COMBATAC study evaluates the the effect as assessed by progression-free survival (PFS) of perioperative systemic chemotherapy including cetuximab and cytoreductive surgery (CRS) and bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis arising from colorectal cancer.
详细描述
More than 10% of patients with colorectal cancer (CRC) already show peritoneal carcinomatosis at the time of initial diagnosis and up to 25% of all patients develop peritoneal carcinomatosis during the natural course of their disease as a common sign of tumor progression or recurrence.
The existing data suggests that CRS and HIPEC as an integral part of a multidisciplinary treatment concept may improve long-term survival of selected patients with peritoneal carcinomatosis of colonic origin. Moreover, hyperthermic peritoneal perfusion with oxaliplatin in combination with synchronous application of 5-FU/leucovorin seems to improve the efficacy of HIPEC in comparison to a mitomycin C-based intraperitoneal treatment regimen and may lead to a better local tumor control. The improved systemic treatment strategy with neoadjuvant chemotherapy may lead to increased rates of complete macroscopic cytoreduction and together with the adjuvant treatment to better control of distant metastasis and tumor recurrence. However, there is no prospective study available evaluating the clinical and oncological outcome after standard-of-care chemotherapy including targeted anticancer therapy in combination with CRS and HIPEC. The published morbidity and mortality rates after CRS and HIPEC are comparable to other major gastrointestinal surgery and seem to be acceptable considering the expected improvement of oncological outcome.
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 71 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Synchronous or metachronous peritoneal carcinomatosis arising from histologically proven colorectal or appendiceal adenocarcinoma
- •Complete macroscopic cytoreduction (CCR-0/1)
- •Free treatment interval of at least 6 month after the last chemotherapy
- •Age over 18 and below 71 years
- •Good general health status (Karnofsky > 70%, ECOG 0-2)
- •Absence of hematogenous metastasis (lung, bone, brain, > 3 peripheric resectable liver metastases)
- •Absence of contraindication for systemic chemotherapy and/or extended surgery
- •Life expectancy greater than 6 months
- •Written informed consent
- •Creatinine clearance > 50 ml/min, serum creatinine ≤ 1.5 x ULN
- •Serum bilirubin ≤ 1.5 x ULN (upper limit of normal), ASAT and ALAT ≤ 2.5 x ULN
- •Platelet count > 100,000 /ml, haemoglobin > 9 g/dl, neutrophile granulocytes ≥ 1,500 /ml, International Normalized Ration (INR) ≤ 2
- •Absence of peripheral neuropathy > grade 1 (CTCAE v4.0)
- •No pregnancy or breast feeding. Adequate contraception in fertile patients.
排除标准
- •Incomplete cytoreduction
- •Hematogenous metastasis including irresectable liver metastasis
- •Prior chemotherapy or therapy with EGFR receptor antibody for metastatic disease
- •K-ras mutation
- •Known allergy to murine or chimeric monoclonal antibodies
- •Histology of signet ring carcinoma
- •Other malignancy than disease under study / second cancer
- •Impaired liver, renal or hematologic function as mentioned above (inclusion criteria)
- •Heart failure NYHA ≥ 2 or significant Coronary Artery Disease
- •Alcohol and/or drug abuse
- •Patients unable or unwilling to comply with the study protocol, treatment or follow-up
- •Patients included in other clinical trials interfering with the present study
研究组 & 干预措施
Treatment Arm
- FOLFOX/FOLFIRI + cetuximab (6 cycles)
- CRS and HIPEC
- FOLFOX/FOLFIRI + cetuximab (6 cycles)
干预措施: CRS (Procedure)
Treatment Arm
- FOLFOX/FOLFIRI + cetuximab (6 cycles)
- CRS and HIPEC
- FOLFOX/FOLFIRI + cetuximab (6 cycles)
干预措施: HIPEC (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 24 months
次要结局
- Overall survival (OS)(5 years)
- Feasibility of the combined treatment concept(9 months)
- Quality of life (QoL)(2 years)
- Pathohistological regression(16 weeks)
研究者
Pompiliu Piso, Prof. MD
Principal Investigator
University of Regensburg