Liver transplantation for patients with colorectal cancer

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

This study is testing if liver transplants can help people with colorectal cancer that has spread to the liver live longer and feel better compared to traditional liver surgery.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oslo University Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Oslo)
• Trial ID: NCT01479608 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the feasibility and outcomes of liver transplantation in patients with colorectal liver metastases (CLM), a condition previously deemed unsuitable for transplantation. The study aims to determine if advancements in surgical techniques and patient selection criteria can improve survival rates for these patients. Participants will be randomized to receive either liver transplantation or liver resection, with a focus on using extended criteria donors. The trial builds on previous findings that suggest improved long-term survival for selected patients with advanced CLM.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically verified adenocarcinoma of the colon or rectum without extrahepatic metastatic disease or local recurrence.

Not a fit: Patients with extrahepatic metastatic disease or those who do not meet the specified health criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly improve survival rates for patients with colorectal liver metastases who are candidates for liver transplantation.

How similar studies have performed: Previous studies have shown promising outcomes for liver transplantation in selected patients with colorectal liver metastases, suggesting that this approach may be viable.

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.

Where this trial is running

Oslo

• Oslo University Hospital — Oslo, Norway (Recruiting)

Study contacts

• Study coordinator: Magnus Smedman, MD

Conditions Colorectal Cancer; Liver Metastasis