PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other)

Overall Status

Completed

CT.gov ID

NCT02086656

Collaborator

(none)

Enrollment

Location

Arm

45.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Capecitabine, oxaliplatin, irinotecan and bevacizumab as perioperative strategy of borderline and/or high risk resectable colorectal cancer liver metastases

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Liver Metastases	Drug: capecitabine, oxaliplatin, irinotecan and bevacizumab	Phase 2

Detailed Description

Previous studies demonstrated a significant association between tumor regression grade of hepatic colorectal metastases (TRG1: complete pathological response; TRG2: major pathological response; TRG3: partial pathological response; versus TRG4-5 no pathological response) and outcome in terms of survival after neoadjuvant treatment. In particular, retrospective data showed an association between oxaliplatin-based chemotherapy and improvement of grade and percentage of tumor regression; moreover, the addition of Bevacizumab seems to improve TRG over chemotherapy alone, conferring also a protection against liver damage due to chemotherapy-induced sinusoidal obstruction syndrome.

This is the rationale that induced us to carry out an evaluation and feasibility assessment of a perioperative approach with COI-B regimen in patients affected by high risk or borderline resectable colorectal liver metastases, with or without previous resection of primary tumor.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES

Actual Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Mar 30, 2017

Actual Study Completion Date :

Mar 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: open label Single arm, open label	Drug: capecitabine, oxaliplatin, irinotecan and bevacizumab perioperative COI-B

Arm

Intervention/Treatment

Experimental: open label

Single arm, open label

Drug: capecitabine, oxaliplatin, irinotecan and bevacizumab

perioperative COI-B

Outcome Measures

Primary Outcome Measures

Pathological response rate [Assessed at the time of surgery of liver metastases (between weeks 17-20 from enrollment)]
Primary: - To evaluate the activity of the regimen with regards to major/complete pathological response. Major/complete pathological response is measured by pathologist in terms of tumor regression grade (TRG) as described by Rubbia-Brandt L, Annals of Oncology 2007 (percentage of vial residual cells 0-10%).

Secondary Outcome Measures

RECIST Response rate [Available at week 9 after enrollment]
- Response rate according to RECIST vers. 1.1 criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion criteria:

Histological diagnosis of colorectal adenocarcinoma.
Liver-limited metastases or metastases mainly (≥80% total disease burden) limited to the liver with extrahepatic disease judged resectable concomitantly or sequentially. Primary tumor may be resected or not, but patient must not be symptomatic for T.
Previous adjuvant therapy is allowed if it had been terminated for at least 6 months.
Previous first line treatment (irinotecan or oxaliplatin containing regimen) with stable or partial response after no more than 3 months of treatment
Age >= 18 years
Performance Status (ECOG <2)
Adequate organ function including the following:
Adequate bone marrow reserve: WBC count >3.0x109/L, absolute neutrophil count

1.5x109/L, platelet count >100x109/L, and hemoglobin >10 g/dL .

Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase < 2.5 xULN
Renal : serum creatinin <2.0xULN
Patients compliance and geographic proximity that allows for adequate follow-up
Patients must sign an informed consent document (ICD)
Male and female patients with reproductive potential must use an approved contraceptive method.

Exclusion Criteria:

Tumor involvement of liver > 75%
Chance of a liver remnant after surgery < 25%
Eligibility for concurrent radiotherapeutic treatment
Disease progression during first line chemotherapy with FOLFOX, XELOX, FOLFIRI or XELIRI plus bevacizumab
Previous treatment with more than 3 months of FOLFOX or FOLFIRI
Previous therapy with bevacizumab or cetuximab or panitumumab
Administration of other experimental drugs during the study.
Body Mass Index > 35
Brain metastases.
Pregnancy and breast-feeding.
Serious or uncontrolled medical pathologies or active infections that would jeopardize the possibility of receiving the investigated treatment. Disorders that could influence the absorption of capecitabine (e.g. malabsorption), intestinal occlusion, Crohn's disease or ulcerative colitis.
Psychiatric disorders, neurologic disease or other conditions that would make it impossible to comply with the protocol procedures. Peripheral neuropathy not related to oxaliplatin previous administration.
Previous dangerous life threatening toxicities from fluoropyrimidine.
Positive anamnesis with regard to other neoplastic diseases except for the ones that have been cured for more than 5 years.