Trans-arterial Treatment of Patients With Intra-hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Overall Survival (OS) at 3 years
研究概览
简要总结
Patients with intrahepatic cholangiocarcinoma (IHC) have relatively aggressive tumors, and the prognosis for most of these patients is dismal. Surgery is the only option that can offer potential cure, but only an estimated 20-25 % are amenable to resection. Down-staging conventional chemotherapy has a relatively low response rate (< 50 %). Patients will be included into the respective treatment arms based on their tumour characteristics and disease stage, but also based on their ability/preferences, as HAI-FUDR/DEX requires going to Oslo every fortnight for the duration of the treatment and SIRT has some limitations regarding tumour distribution.
Data from the MSKCC has suggested a clinically relevant benefit from adding intrahepatic chemotherapy to systemic therapy. HAI-FUDR/DEX is not approved in Norway and can only be evaluated in a protocolized trial. Given the risk of distant disease progression with IHC, the addition of conventional systemic chemotherapy makes good clinical sense, and data from MSKCC supports this approach. SIRT is another modality also applied trans-arterially and directly into the tumour. This treatment is approved in Norway and available in Bergen and in Oslo. It is far less cumbersome to deliver and maintain than HAI-FUDR/DEX. The efficacy and safety of the two treatment groups, HAI-FUDR/DEX and SIRT, will be compared in a parallel cohort (non-randomized) design
详细描述
This is a parallel (twin) cohort study aiming to assess the efficacy and safety of selective internal radiation therapy (SIRT) and hepatic artery infusion (HAI) with floxuridine (FUDR) and dexamethasone (DEX) in combination with modern systemic chemotherapy. The study groups will consist of patients with intrahepatic cholangiocarcinoma (IHC) not amenable to surgical resection.
Thus, for many patients with IHC, effective treatment options are limited. Liver-directed hepatic arterial chemotherapy delivered through a surgically implanted HAI pump has been evaluated in several small series and appears to have greater efficacy than systemic therapy alone. Although used predominantly in patients with hepatic colorectal metastases, HAI chemotherapy has shown efficacy in patients with primary liver cancer. HAI-FUDR/DEX is not approved in Norway (nor the EU), but is used in an ongoing RCT at Oslo University Hospital for the treatment of colorectal cancer liver metastases (CRLM) (Excalibur).
Based on the tumor characteristics and tumor stage, as well as the patient's ability to undergo HAI-FUDR/DEX treatment, we will divide patients who are not amenable to upfront resection but who are potentially curable, into two down-staging treatment groups: systemic chemotherapy in combination with either SIRT or HAI with FUDR/DEX. If allocated to SIRT, a standard work-up is performed in Oslo, with SIRT being performed at the same site 1-3 weeks later.
Trans-arterial treatment modalities If allocated to HAI-FUDR/DEX, a laparotomy is scheduled within three weeks from inclusion. Upon laparotomy, hilar lymph nodes are cleared completely and cholecystectomy is performed. Placement of The Tricumed IP2000V pump and catheter will be as per current routine. The patient is expected to stay at the hospital ward for 3-6 days after the pump is implanted. During this time they will undergo a standard control of catheter patency and absence of any collateral which is performed by direct angiography and isotope scanning 3-5 days post surgery.
The Tricumed IP2000V pump is used outside its approved indication, and experience is limited to other clinical trials using the HAI pump for administration of FUDR. The Tricumed IP2000V pump is a constant flow implantable infusion pump intended to store and slowly deliver FUDR/DEX intrahepatically. The infusion pump is contoured with smooth radius to increase the comfort for patients. It contains a fluid reservoir in the form of a titanium bellow that is pressurized by n-butane at constant pressure. The n-butane is in phase change between a liquid and a vapor and at body temperature of 37 °C provides a constant pressure of 2.5 bar. The body temperature of the patient provides the system with energy. This drive system provides the implantable infusion pump with an inexhaustible source of energy. The drug therapy is therefore delivered at a substantially constant rate over the whole refill interval. Through use of a gaseous drive medium, arduous warming up of the implantable infusion pump is no longer necessary before implantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Intra-hepatic cholangiocarcinoma. Diagnosis confirmed by biopsy, cytology or previous resection.
- •Not amenable for upfront resection. Defined as:
- •A tumour that is technically not resectable with R0 margins (i.e. where resection will not yield an FLR of sufficient size and function) without reconstruction of portal or liver vein, or artery.
- •Any multifocality (more than one tumour) irrespective of distance between assumed primary and other lesions
- •Recurrent tumour following resection
- •Radiologically or cytology-proven malignant regional lymph nodes
- •Disease confined to the liver or associated with limited, resectable porta hepatis lymph node metastases
- •Radiologically measurable disease with at least one lesion > 2 cm in greatest diameter
- •Physical performance score WHO/ECOG stage 0/1
- •Age > 18 years
- •Assumed ability to tolerate at least one full cycle of GemOx
- •For eligibility to HAI-FUDR/DEX treatment, patients must be willing and able to go to Oslo every fortnight
- •Women of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study, as defined in this protocol. Male patients or male patients who have female partners of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study, as defined in this protocol. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
排除标准
- •Any non-liver malignant deposit (except for resectable, hilar lymph nodes)
- •Serum bilirubin, creatinine or INR outside of normal range
- •Haemoglobin < 7 g/dL and thrombocytes < 75 × 109/L
- •Liver failure (if cirrhosis, Child-Pugh B or C)
- •Clinical evidence of portal hypertension (non-surgically related ascites, gastro-oesophageal varices, portal vein thrombosis)
- •History of peripheral neuropathy
- •More than 70 % of liver consisting of tumour
- •History of other malignancy past three years except localized/early stage cancer that has been adequately resected.
- •Pregnant or lactating women
- •Expected life expectancy less than three months.
- •Inability to comply with study routines or follow-up procedures
- •Inability to read and comprehend Norwegian
- •Arterial anatomy unsuited for SIRT or HAI, respectively
- •Any reason why, in the view of the investigators, the patient should not be included
研究组 & 干预措施
Hepatic artery infusion (HAI) chemotherapy
Liver-directed hepatic arterial chemotherapy delivered through a surgically implanted HAI-pump has been evaluated in several small series and appears to have greater efficacy than systemic therapy alone.
干预措施: Floxuridine (Drug)
Selective Internal Radiation Therapy (SIRT)
SIRT is approved in Norway, however, usen in a limited degree. Recent research in hepatocellular carcinoma has shown the importance of personalized dosimetry to obtain high tumour radiation dose, while limiting the dose to surrounding liver tissue, yielding improved response and survival (Dosisphere study), It is likely that these findings can be applied also to cholangiocarcinoma.
干预措施: Selective Internal Radiation Therapy (SIRT) (Procedure)
结局指标
主要结局
Overall Survival (OS) at 3 years
时间窗: 3 years
The study will assess whether the combination of systemic chemotherapy (current standard) with either SIRT or HAI-FUDR/DEX for patients not amendable to upfront resection may increase the possibility for later resection nad/or prolong survival.
次要结局
- Tumor response(from date of inclusion and every 8 weeks (after each cycle of chemotherapy), until death or tumor progression, up to 156 weeks (3 years))
- Quality of Life by using EORTC QLQ-C30(From date of inclusion, and every 8 weeks until death or other illness-related incident. Up to 156 weeks (3 years))
- Quality of Life by using EQ-5D-5L(From date of inclusion, and every 8 weeks until death or other illness-related incident. Up to 156 weeks (3 years))
- Assess the resection rate following downstaging(3 years)
- Assess complications, toxicity and side effects in treatment groups(Within 30 days of surgery, then at every clinic visit (every 2 weeks) until death or other illness-related incident. Up to 156 weeks (3 years))
- Assess circulating cell-free (ctDNA) before and after treatment and correlate with treatment outcomes(At date of inclusion, at week 8, at week 16 and at end-of-trial (3 years).)
研究者
Kristoffer Lassen
Principal Investigator, Head of Department of HPB-surgery at Oslo University Hospital, MD, PHD,
Oslo University Hospital