18 Years
75 Years
Both
Overall Survival, Progression Free Survival
Trial Information
Attempts of liver transplantation for CRC liver metastases are registered in the European
Liver Transplant Registry (ELTR). During 1977 to 1995 survival data representing 45
patients, show a 1, 3 and 5-year survival rate of 73%, 36% and 18%, respectively(post
transplantation immunosuppression with the antiproliferative agent rapamycin was not in
regular use at that time). Historical data and have shown that more than 49% of 25 patients
transplanted in Vienna for CRC liver metastases died of non-cancer related causes.
In 2006 we acquired an ethical approval (S-05409 Regional Ethics Committee, Helse Sor-Ost)
for a clinical pilot study (SECA-study) to investigate Ltx for treatment in selected CRC
patients with non-resectable liver metastases, using the mTOR inhibitor Rapamycin as
standard immunosuppression from postoperative day 1. The ethical authorization was to
conduct an open labeled, non-randomized study for up to 25 patients. By January 1st. 2010,
16 patients have been transplanted in the study. All of the patients had advanced metastatic
disease and had received palliative chemotherapy. Patients included in the study had liver
metastasis only and was not eligible for liver resection at the time of Ltx.
Fifteen of the patients are alive at 2-37 months follow-up. One patient with massive tumor
load (4.6 kg) in the liver and overgrowth to the diaphragm (detected by explanting the
liver) developed recurrence in the transplanted liver at 2 month post transplantation and
departed 4 months later. The patients that are alive have excellent health related quality
of life (QOL) measured with EORTC QLQ-C30 (at 1, 3, 6, 12 and 18 months post transplant). As
expected, many patients have experienced recurrence of the disease, mainly to the lungs.
Preliminary data from the SECA pilot study indicate that Ltx is feasible in selected
patients with non-resectable liver metastases from CRC and the perioperative mortality is
0%. Still, it is important to recognize that Ltx is a major procedure with several potential
life threatening complications.
Inclusion Criteria:
- Histologically verified adenocarcinoma in colon or rectum with pathological
classification as pN0 or pN1 disease.
- Liver metastases not eligible for curative liver resection. Before start of
chemotherapy, no lesion should be larger than 8 cm and total number of lesions should
be 10 or less.
- At least 10% response (RECIST-criteria) on evaluation after 3-4 cycles of 1. line
chemotherapy and patients must be randomized before evaluation after 8 cycles of
chemotherapy.
- Patients with CEA levels above 30 ng/ml at time of start of chemotherapy should have
a reduction in CEA of at least 50% after 3-4 cycles.
- No signs of extra hepatic metastatic disease or local recurrence according to PET/CT
scan.
- CEA<100 ng/ml at time of primary diagnosis as well as at time of metastatic disease.
- No signs of extra hepatic metastatic disease or local recurrence according to CT or
MR (thorax/abdomen/pelvis) scan within 4 weeks prior to the faculty meeting at the
transplant unit
- No signs of local recurrence judged by colonoscopy within 12 months prior to the
faculty meeting at the transplant unit
- Age 18-70 years
- Performance status, ECOG 0 or 1.
- Satisfactory blood tests Hb >10g/dl, neutrophiles >1.0 (after any G-CSF), TRC >75,
Bilirubin<2 x upper normal level, ALP< 3 x upper normal level, ASAT,ALAT<5 x upper
normal level, Creatinine <1.25 x upper normal level. Albumin above lower normal
level.
- Circumferential resection margins (CRM) at least >2mm.
- Signed informed consent.
Exclusion Criteria:
- Weight loss >10% the last 6 months
- Patient BMI > 30
- Known hypersensitivity to rapamycin
- Other contraindications for liver transplantation
- Other malignancies
- Prior organ transplant
- Women who are pregnant or breast feeding
- Patients, which according to the project group, will not benefit from the treatment
or are considered not able to complete treatment according to protocol
- Prior extra hepatic metastatic disease or local relapse
- Liver metastases detected within 12 months of diagnosis of rectal cancer.
- Patients who have not received standard preoperative or postoperative treatment for
the primary CRC tumour.
- Patients who have not received standard surgical treatment of the primary CRC tumour.
- Perineural invasion
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Time Frame:
3 years
Safety Issue:
Yes
Authority:
Norway: Regional Ethics Committee
Study ID:
2010/2856a (SECA II)
NCT ID:
NCT01311453
Start Date:
February 2011
Completion Date:
September 2019
Related Keywords:
- Overall Survival
- Progression Free Survival
- Colorectal cancer
- Liver mets
- Liver transplantation
- Colorectal Neoplasms
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