Clinical trial NCT01293942: IXO+A in mCRC With Liver-only Metastases
Official title: A Single-arm Phase II Downsizing Study of Irinotecan, Capecitabine and Oxaliplatin (IXO) and Bevacizumab as First-line Treatment to Assess Conversion to Resectability of Liver-only Metastases in Colorectal Cancer Patients With Initially Unresectable Metastases
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: unresectable liver-only metastases in colorectal cancer
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: Sanofi
First posted: 2011-02-11
Enrollment: 0
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: The percentage of patients with defined unresectable metastatic disease who will benefit from a first-line treatment enabling secondary complete metastasectomy is unknown but limited. Definition of optimized treatment algorithms is difficult due to very inhomogeneous patient populations.

This open label, multicentre Phase II study primarily aims to assess the resection rate achievable in a selected patient population with initially unresectable metastatic disease limited to the liver only in order to evaluate feasibility, safety and efficacy with regards to secondary resection of hepatic lesions in these patients.

The trial aims to enrol only patients meeting defined criteria of unresectability with regards to their hepatic lesions and will exclude patients with extrahepatic lesions in order to examine the most appropriate, highly active treatment regimen for this group of unresectable patients with the highest probability of a successful secondary metastasectomy with curative intent. The trial will be conducted in highly specialized centres with a track record of successful interdisciplinary treatment approaches in the field of metastatic colorectal cancer to allow the precise assessment of the peri-operative safety parameters as well as an evaluation of the surgical treatment approaches.

The IXO regimen selected for this study has shown in a phase I/II study promising efficacy and a favourable safety profile. Bevacizumab has demonstrated a significant survival benefit in combination with chemotherapy in metastatic colorectal cancer. Therefore the study will allow evaluation of its potential benefit in combination with the two most active current chemotherapy regimens in the first-line and post-operative treatment setting.


Eligibility criteria: Inclusion Criteria:

* Primary colorectal cancer with unresectable metastatic lesion(s)
* At least one measurable lesion, confirmed by CT scan
* Male and female patients, aged ≥ 18 years
* ECOG performance score of 0 or 1 (within 1 week of study treatment start)
* Written informed consent
* Adequate general condition, cardiopulmonary functions and performance status
* Liver metastases no initially foreseen R0 resection of all hepatic lesions, but deemed potentially resectable after response to downsizing therapy

Exclusion Criteria:

* Extrahepatic metastatic disease
* Prior systemic or local treatment for metastatic disease, prior therapy with a biologic agent, prior adjuvant or neo-adjuvant chemotherapy, prior radiotherapy to the liver, other concurrent chemotherapy
* Inadequate bone marrow, liver, renal function, uncontrolled hypertension
* Pregnancy or lactation

Primary outcomes:
measure: conversion to resectability during downsizing therapy with IXO+A patients with initially unresectable liver-only metastases associated with colorectal cancer
timeFrame: after 8 IXO+A cycles
Secondary outcomes:
measure: Recurrence-free survival (RFS)
timeFrame: Every 2 cycles
measure: Progression-free survival (PFS)
timeFrame: Every 2 cycles
measure: Time to response (TTR)
timeFrame: Every 2 cycles
measure: Overall survival (OS)
timeFrame: Every 2 cycles
measure: Pathological complete response (pCR) rate
timeFrame: assessed post-operatory
measure: Overall response rate (ORR)
timeFrame: Every 2 cycles
measure: Number of participants with Adverse Events as a measure of Safety and Tolerability
timeFrame: Every 3 weeks
measure: Surgical safety (frequency of surgical complications)
timeFrame: assessed post-operatory
measure: Pathological changes in the non-tumoural liver following therapy with IXO+A
timeFrame: assessed post-operatory
measure: R0, R1, R2 resection rate after up to 8 cycles of downsizing therapy with IXO+A
timeFrame: assessed post-operatory
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: The Ottawa Hospital Cancer Centre
name: Jean Maroun, MD
role: STUDY_CHAIR
References: