Study of Immune Response and Liver Damage Induced by Chemotherapy for Liver Metastases of Colorectal Cancer

NCT ID: NCT01673607

Last Updated: 2021-09-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-11
• Study Completion Date: 2023-03-31

Brief Summary

The immune response at primary tumor has a major role in the prognosis of colorectal cancer (CRC). Some studies suggest a prognosis value of cytotoxic T cell and memory T cells at primary tumor greater than tumoral stage. There is no work in the literature that has examined the prognosis value of the immune response in liver metastases. To study immune cells (histology) and inflammatory response (cytokines) in liver metastases is a challenge to understand the effectiveness of chemotherapy used in this situation.

The chemotherapy used in liver metastases of colorectal cancer also have effects on non-tumoral liver tumor and therefore can interfere with postoperative complications of hepatic resection. Sinusoidal dilatation is present in 20% to 80% of patients who received oxaliplatin before hepatectomy. Steatosis is frequently observed after administration of 5-FU alone or in combination with irinotecan. This steatosis may also be accompanied by inflammatory lesions (steatohepatitis), especially after administration of oxaliplatin or irinotecan and is associated with increased postoperative mortality. The hepatic toxicity of new biological agents is not well known (cetuximab and bevacizumab). The mechanisms of chemotherapy-induced toxicities are currently unknown. The main objective is to analyze the profile of the immune response in liver metastases of CRC and find the link with the radiological response. Measurements will be made by quantitative RT-PCR on frozen liver biopsies. Secondary objective is to seek a correlation between the histological lesions induced by chemotherapy and non-invasive tests for liver fibrosis. The secondary endpoints are rate of immune cells, histologic response (percentage of tumor necrosis), disease-free survival, the non-invasive test of fibrosis, the chemotherapy-induced liver injury, cytokines and circulating angiogenic factors.

Conditions

Resectable Hepatic Metastases of Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT

Interventions

Biopsie liver

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

Patient older than 18 years.

• Patients with histologically proven colorectal cancer with resectable or potentially resectable liver metastases.
• First line chemotherapy alone or combination with intravenous 5FU, oral 5FU (capecitabine), oxaliplatin, irinotecan, cetuximab, panitumumab or bevacizumab (LV5FU2, XELODA, FOLFIRI, FOLFOX, XELOX, XELIRI alone or in combination with either cetuximab or panitumumab or bevacizumab).
• Signature of informed consent.
• Patient affiliated to French Social Security.

Exclusion Criteria

Patients taking immunosuppressive therapy.

• Lack of measurable tumoral target.
• Patients with a contre-indication of all chemotherapy used: oxaliplatin, irinotecan, fluorouracil, capecitabine, cetuximab, panitumumab, bevacizumab.
• Patients hospitalized without consent.
• Patients in emergency situations.
• Patients under guardianship.
• Patients deprived of their liberty by judicial or administrative procedure.
• Pregnant or nursing women, women without effective contraception.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Poitiers University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Poitiers University Hospital

Poitiers, , France

Site Status: RECRUITING

Countries

France

Central Contacts

David TOUGERON, MD

Role: CONTACT

david.tougeron@chu-poitiers.fr

33.5.49.44.37.51

Facility Contacts

David TOUGERON, MD

Role: primary

david.tougeron@chu-poitiers.fr

33.5.49.44.37.51

Other Identifiers

METAHEP

Identifier Type: -

Identifier Source: org_study_id