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

Colorectal Cancer Liver Metastases Clinical Trial

— COI-B  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02086656
• Other study ID #: COI-B
• Status: Completed
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: March 30, 2017

Study information

• Verified date: August 2019
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: March 30, 2017
• Est. primary completion date: March 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer Liver Metastases
• Colorectal Neoplasms
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

Drug:
• capecitabine, oxaliplatin, irinotecan and bevacizumab
perioperative COI-B

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milan	Mi

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological response rate	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%).	Assessed at the time of surgery of liver metastases (between weeks 17-20 from enrollment)
Secondary	RECIST Response rate	- Response rate according to RECIST vers. 1.1 criteria	Available at week 9 after enrollment