Clinical trial NCT02086656: PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES
Official title: PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer Liver Metastases
Keywords: liver metastases
colorectal cancer
perioperative treatment
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological response rate
timeFrame: Assessed at the time of surgery of liver metastases (between weeks 17-20 from enrollment)
Secondary outcomes:
measure: RECIST Response rate
timeFrame: Available at week 9 after enrollment
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
state: Mi
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Filippo de Braud, MD
role: PRINCIPAL_INVESTIGATOR
References: