No registrations found.
ID
Source
Brief title
Health condition
irresectabel colorectal livermetastases, colorectale levermetastasen
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Response rate expressed by RECIST criteria, after two percutaneous liver perfusions with melphalan at a six week interval;
• Number of curative resections after percutaneous perfusion.
Secondary outcome
• Safety of percutaneous liver perfusions with the Delcath 2nd generation system;
• Overall survival and overall progression free survival;
• Duration of response and duration of stable disease;
• Quality of life.
Background summary
Malignancies of the liver are the third most important cause of cancer-related deaths in the world. This kind of cancer can be primary (origin in the liver) of secondary (metastases from another part of the body). The most common form of primary liver cancer is the hepatocellular carcinoma (HCC) en the most common form of secondary liver cancer are metastases of colorectal carcinoma (CRCLM). About 30-50% of all patients with colorectal cancer, develop liver metastases synchronous: 14.5-25%, metachronous: 14.5-25%).
Patients with liver metastases of colorectal carcinoma often have a bad prognosis, and for these patients surgical resection is the only curative option, despite the constant innovations in chemotherapy. The surgical treatment offers an acceptable morbidity, mortality and the 5-year survival is around 40-50%. Unfortunately only 20-25% of the patients with CRCLM qualify for surgery. The other patients can only be treated with chemotherapy. A part of the patients treated with chemotherapy and with initially irresectable metastases, become operable because of the response to chemotherapy. The disadvantage of systemic administration of chemotherapy in the treatment of liver metastases is that, because of systemic toxicity, the maximum tolerated dose is reached earlier than the minimum effective dose. To accomplish better results with patients with irresectable metastases confined to the liver, isolated hepatic perfusion ( IHP) has been developed. The principle of IHP is to shut the liver off of the systemic circulation by performing an operation. Subsequently the liver is flushed for an hour with a very high dose of chemotherapy, which would be toxic and lead to fatal complications when administered systemic. Then the liver is connected to the systemic circulation again. Because this procedure is associated with considerable morbidity (20%) and mortality (7%), a new procedure was developed by Delcath in which the hepatic perfusion can be performed percutaneous. Expected is that both morbidity and mortality will decrease significantly. In addition, this procedure can be performed several times.
Study objective
Percutaneous chemosaturation of only the liver in patients with irresectabe colorectal metastases will be safe and effective and lead to downstaging of the tumor andprevent systemic toicity
Study design
• After 6 weeks;
• Every 3 months in the first year;
• Then once a half year;
Intervention
Percutaneous isolated hepatic perfusion/chemosaturation of the liver; The principle of IHP is to shut the liver off of the systemic circulation by performing an operation. Subsequently the liver is flushed for an hour with a very high dose of chemotherapy, which would be toxic and lead to fatal complications when administered systemic. Then the liver is connected to the systemic circulation again.
Inclusion criteria
- Liver metastases of histologically confirmed primary colorectal adenocarcinoma;
- Resection of primary tumor > 1 month before IHP;
- Irresectable metastases confined to the liver based on CT-Thorax/abdomen and PET imaging;
- Metastases measurable on CT-scan;
- Informed consent;
- Life expectancy > 4 months;
- Leukocytes ≥ 3.0 X 10^9/L;
- Thrombocytes ≥ 100 X 10^9/L;
- Creatinine clearance ≥ 40 ml/min;
- Bilirubin <17 µmol/L;
- APTT < 32.5 sec;
- PT < 13.7 sec;
Exclusion criteria
Biological age <18 and >65 years
- WHO performance status ≥ 2 (Appendix A);
- < 40% healthy liver tissue;
- Aberrant vascular anatomy, which impedes IHP (e.g. aberrant right or left hepatic artery, severe atherosclerosis, vascular dissections);
- Severe comorbidity (e.g. cardiovascular disease, diabetes with nephropathy, active infections, other liver disease);
- Incompetent / Mentally disabled;
- Pregnancy, inadequate anticonception.
Design
Recruitment
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL3888 |
| NTR-old | NTR4050 |
| CCMO | NL45013.058.13 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |
| OMON | NL-OMON41379 |