Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
P130922
- NCT ID:
NCT02597348
Conditions
- Liver Metastasis
- Colorectal Cancer
- Metastasis
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Liver Transplantation | Experimental | Arm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices). | |
No intervention | No Intervention | Arm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM. | |
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)
- ≤ 2 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
Maximum Eligible Age: | 65 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 5 years overall survival (OS) |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | 3-years overall survival (OS) |
Time Frame: | 3 years |
Safety Issue: | |
Description: | |
Measure: | Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C) |
Time Frame: | 3 and 5 years |
Safety Issue: | |
Description: | |
Measure: | Recurrence rate at 3 and 5 years |
Time Frame: | 3 and 5 years |
Safety Issue: | |
Description: | Radiological assessment will be performed according to the RECIST criteria and confirmed by 2 local radiologists. |
Measure: | Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30 |
Time Frame: | year 5 |
Safety Issue: | |
Description: | QLQ-C30 covers general aspects of health-related quality of life |
Measure: | Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21 |
Time Frame: | year 5 |
Safety Issue: | |
Description: | QLQ-LMC21 is valid and reliable questionnaire module to use with the QLQ-C30 in assessing in hepatectomy or palliative treatment for colorectal liver metastases |
Measure: | Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database |
Time Frame: | year 5 |
Safety Issue: | |
Description: | |
Details
Phase: | N/A |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Assistance Publique - Hôpitaux de Paris |
Trial Keywords
- Liver
- Metastasis
- Colorectal cancer
- Liver transplantation
Last Updated
August 3, 2021