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Liver Transplantation and Colorectal Cancer

Primary Purpose

Colorectal Cancer, Liver Metastasis

Status
Recruiting
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Liver transplantation and liver resection
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically verified adenocarcinoma in colon or rectum.
  • No signs of extra hepatic metastatic disease or local recurrence according to PET/CT scan.
  • 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 / CT colography within 12 months prior to the faculty meeting at the transplant unit
  • Good 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, ASAT,ALAT<5 x upper normal level, ,Creatinine <1.25 x upper normal level. Albumin above lower normal level.
  • Standard surgical procedure with adequate resection margins including circumferential resection margins (CRM) of at least ≥2mm for rectal cancer patients.
  • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to GCP, and national/local regulations.
  • Received at least 3 cycles of chemotherapy (6 weeks of treatment), with no increase in size of the lesions according to RECIST-criteria

Additional inclusion criteria for patients included in part A:

- Six or more liver metastases technically resectable

Additional inclusion criteria for patients included in part B:

  • Metachronous liver metastases (more than 12 months from diagnosis of CRC and/or end of adjuvant treatment)
  • Pathological classification of primary tumor as pN0 disease.
  • CEA<100 ng/ml at time of primary diagnosis as well as at time of diagnosis of metastatic disease.
  • Liver metastases not eligible for curative liver resection.
  • Before start of 1. line chemotherapy, no lesion should be larger than 10 cm and total number of lesions should be 20 or less.
  • At least 10% response (RECIST-criteria) on 1. line chemotherapy. Patients must be accepted for transplantation before progressive disease on 1. line chemotherapy.

Additional inclusion criteria for patients included in part C:

  • Liver metastases not eligible for curative liver resection.
  • Received 1.line treatment.
  • Before start of 2. or 3. line chemotherapy, no lesion should be larger than 10 cm and total number of lesions should be 20 or less.
  • At least 10% response (RECIST-criteria) on 2. or 3. line chemotherapy. Patients must be accepted for transplantation before progressive disease on 2. or 3. line chemotherapy.
  • Two years or more time span from the CRC diagnosis and date of being listed on the transplantation list.

Additional inclusion criteria for patients included in part Arm D:

Patients with expected overall survival of 6-12 months without a liver transplant.

The patient might be included without further chemotherapy treatment. Patients may have resectable pulmonary lesions at time of inclusion in the present study.

Exclusion Criteria:

  • Weight loss >10% the last 6 months
  • Patient BMI > 30
  • Other malignancies
  • Prior extra hepatic metastatic disease or local relapse.
  • Patients who have not received standard pre-operative, per-operative or post-operative treatment for the primary CRC.
  • Palliative resection of primary CRC tumor.
  • Previous randomization in this trial.
  • Any reason why, in the opinion of the investigator, the patient should not participate.

Sites / Locations

  • Oslo University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

A: Transplantation or resection (randomized)

B: Liver transplantation

C:Liver transplantation

D:Liver transplantation

Arm Description

Liver transplantation or liver resection by 1:1 randomization (open label)

For non-resectable patients metachronous disease.

For non-resectable patients synchronous disease.

For non-resectable patients synchronous disease.

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

Full Information

First Posted
November 22, 2011
Last Updated
October 4, 2022
Sponsor
Oslo University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01479608
Brief Title
Liver Transplantation and Colorectal Cancer
Official Title
A Randomized Controlled Clinical Trial to Evaluate the Benefit and Efficacy of Liver Transplantation as Treatment for Selected Patients With Liver Metastases From ColoRectal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2012 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Colorectal liver metastases (CLM) are currently considered an absolute contraindication for liver transplantation (Lt) although Lt for other primary and secondary liver malignancies show excellent outcome in selected patients. Before 1995, several Lts for CLM were performed, but the outcome was poor (18% 5-year survival) and Lt for CLM was stopped. Since then, several advances have been achieved and survival following Lt has improved by almost 30%. Thus, a 5-year survival of about 50% following Lt for CLM could be anticipated. The investigators have previously included 21 patients in a pilot study. All patients had advanced CLM at the time of Lt. Long term overall survival (OS) exceeds by far previously reported outcome for this patient group and is comparable or better than survival following repeat Lt for non-malignant diagnoses. Development of robust selection criteria may further improve the results. The investigators will conduct a randomized controlled trial to explore whether liver transplantation in selected patients with liver metastases from CRC can obtain significant life extension and better health related quality of life compared to patients receiving surgical resection. The investigators will also explore if patient selection according to nomo-grams for outcome of colorectal cancer can define a subgroup of patients with a 5 year survival of at least 50% or even cure from the disease.
Detailed Description
Arm D: use of extended criteria donors (ECD)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A: Transplantation or resection (randomized)
Arm Type
Experimental
Arm Description
Liver transplantation or liver resection by 1:1 randomization (open label)
Arm Title
B: Liver transplantation
Arm Type
Experimental
Arm Description
For non-resectable patients metachronous disease.
Arm Title
C:Liver transplantation
Arm Type
Experimental
Arm Description
For non-resectable patients synchronous disease.
Arm Title
D:Liver transplantation
Arm Type
Experimental
Arm Description
For non-resectable patients synchronous disease.
Intervention Type
Procedure
Intervention Name(s)
Liver transplantation and liver resection
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically verified adenocarcinoma in colon or rectum. No signs of extra hepatic metastatic disease or local recurrence according to PET/CT scan. 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 / CT colography within 12 months prior to the faculty meeting at the transplant unit Good 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, ASAT,ALAT<5 x upper normal level, ,Creatinine <1.25 x upper normal level. Albumin above lower normal level. Standard surgical procedure with adequate resection margins including circumferential resection margins (CRM) of at least ≥2mm for rectal cancer patients. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to GCP, and national/local regulations. Received at least 3 cycles of chemotherapy (6 weeks of treatment), with no increase in size of the lesions according to RECIST-criteria Additional inclusion criteria for patients included in part A: - Six or more liver metastases technically resectable Additional inclusion criteria for patients included in part B: Metachronous liver metastases (more than 12 months from diagnosis of CRC and/or end of adjuvant treatment) Pathological classification of primary tumor as pN0 disease. CEA<100 ng/ml at time of primary diagnosis as well as at time of diagnosis of metastatic disease. Liver metastases not eligible for curative liver resection. Before start of 1. line chemotherapy, no lesion should be larger than 10 cm and total number of lesions should be 20 or less. At least 10% response (RECIST-criteria) on 1. line chemotherapy. Patients must be accepted for transplantation before progressive disease on 1. line chemotherapy. Additional inclusion criteria for patients included in part C: Liver metastases not eligible for curative liver resection. Received 1.line treatment. Before start of 2. or 3. line chemotherapy, no lesion should be larger than 10 cm and total number of lesions should be 20 or less. At least 10% response (RECIST-criteria) on 2. or 3. line chemotherapy. Patients must be accepted for transplantation before progressive disease on 2. or 3. line chemotherapy. Two years or more time span from the CRC diagnosis and date of being listed on the transplantation list. Additional inclusion criteria for patients included in part Arm D: Patients with expected overall survival of 6-12 months without a liver transplant. The patient might be included without further chemotherapy treatment. Patients may have resectable pulmonary lesions at time of inclusion in the present study. Exclusion Criteria: Weight loss >10% the last 6 months Patient BMI > 30 Other malignancies Prior extra hepatic metastatic disease or local relapse. Patients who have not received standard pre-operative, per-operative or post-operative treatment for the primary CRC. Palliative resection of primary CRC tumor. Previous randomization in this trial. Any reason why, in the opinion of the investigator, the patient should not participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Magnus Smedman, MD
Phone
23026600
Ext
47
Email
torha@ous-hf.no
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0451
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Magnus Smedman, MD
Phone
23026600
Ext
47
Email
torha@ous-hf.no

12. IPD Sharing Statement

Citations:
PubMed Identifier
23360920
Citation
Hagness M, Foss A, Line PD, Scholz T, Jorgensen PF, Fosby B, Boberg KM, Mathisen O, Gladhaug IP, Egge TS, Solberg S, Hausken J, Dueland S. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013 May;257(5):800-6. doi: 10.1097/SLA.0b013e3182823957.
Results Reference
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Liver Transplantation and Colorectal Cancer

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