Clinical trial NCT02597348: Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy
Official title: Curative Potential of Liver Transplantation in Patients With Definitively Unresectable Colorectal Liver Metastases (CLM) Treated by Chemotherapy: a Prospective Multicentric Randomized Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Liver Metastasis
Colorectal Cancer
Metastasis
Keywords: Liver
Metastasis
Colorectal cancer
Liver transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-11-05
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicentric randomized parallel group open trial comparing 5-year survival of chemotherapy followed by LT (Group LT+C) versus chemotherapy alone (Group C) in patients with confirmed unresectable liver-only metastases, well controlled by chemotherapy (no progression) and extensively explored by modern imaging techniques. The primary objective of the trial is to validate in a large multicentric cohort of selected patients the possibility to obtain at least 50% 5-years survival with LT combined to chemotherapy compared to around 10% with chemotherapy alone.

Detailed description: Liver transplantation (LT) has recently been proposed as alternative treatment for definitively unresectable colorectal liver metastases in selected patients with a 60% estimated survival at 5 years in a recent prospective Norwegian study. However, disease free survival (DFS) in this preliminary study has been poor with 90% of recurrence after LT.

The objective of our study is to validate LT as a therapeutic option on a large multicentric scale throughout a highly strict policy selection in term of survival, disease free survival and quality of life. In order to reduce selection bias, unresectability criteria and theorical indication to LT will be confirmed by an independent Steering Committee including HPB surgeons, oncologists, radiologists and hepatologists.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 and ≤ 65 years
* Good performance status, ECOG 0 or 1 (39).
* Histologically proved adenocarcinoma in colon or rectum
* BRAF wild-type CRC on primary tumor or liver metastases
* High standard oncological surgical resection of the primary defined by :

  * Safe margin of resection
  * Curative resection of primary tumor according to oncological principles
  * TNM adequate staging
* Absence of local recurrence on colonoscopy performed in the 12 months prior to inclusion (except in case of primary tumor resection \< 12 months )
* Confirmed non resectable colorectal liver metastases by the validation committee
* ≥ 3 months of tumor control during the last chemotherapy line: Stable or Partial Response on RECIST criteria (40)
* ≤ 3 lines of chemotherapy for metastatic disease
* CEA \< 80 microg/L or a decrease ≥ 50% of the highest serum CEA levels observed during the disease
* Absence of extrahepatic tumor localisation according to CT scan and PET-CT
* Renal function should be within the normal limits
* No need for extra-renal purification procedure, hemodialysis or kidney transplantation associated (nephrologist assessment)
* A platelet count\> 80,000 / mm3
* White blood cell count\> 2500 / mm3
* Eligible for both treatments groups
* Signed informed consent and expected cooperation of the patient for the treatment and follow up

Exclusion Criteria:

* Participation refusal
* No health insurance facilities
* General contraindication to LT (Severe cardiopulmonary disease or other life-limiting coexisting medical conditions, extrahepatic malignancy, active alcohol or substance abuse, active infection or uncontrolled sepsis, lack of psychosocial support or inability to comply with medical treatment)
* Other malignancies either concomitant or within 5 years before liver transplantation
* Patients not having received standard treatment for the primary CRC according to recommended guidelines
* Prior extra hepatic metastatic disease or local relapse
* Pregnancy at the time of inclusion

Primary outcomes:
measure: 5 years overall survival (OS)
timeFrame: 5 years
Secondary outcomes:
measure: 3-years overall survival (OS)
timeFrame: 3 years
measure: Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)
timeFrame: 3 and 5 years
measure: Recurrence rate at 3 and 5 years
timeFrame: 3 and 5 years
measure: Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30
timeFrame: year 5
measure: Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21
timeFrame: year 5
measure: Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database
timeFrame: year 5
Other outcomes:
Locations:
city: Villejuif
country: France
facility: AP-HP, Paul Brousse Hospital
Study officials:
affiliation: AP-HP, Paul Brousse Hospital
name: René ADAM, PhD
role: PRINCIPAL_INVESTIGATOR
References: