IXO+A in mCRC With Liver-only Metastases

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01293942
• Other study ID #: OTT 10-01
• Status: Withdrawn
• Phase: Phase 2
• First received: February 8, 2011
• Last updated: June 4, 2013
• Start date: March 2011
• Est. completion date: February 2012

Study information

• Verified date: June 2013
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• irinotecan, capecitabine, oxaliplatin (IXO) and bevacizumab
IXO plus bevacizumab regimen is given every 3 weeks (Q3W), in the following order: Bevacizumab (A): 7.5 mg/kg via IV infusion, day 1 Oxaliplatin (O): 100 mg/m2 via 2-hour IV infusion, day 1 Irinotecan (I): 160 mg/m2 via 1-hour IV infusion, day 1 Capecitabine (X): 950 mg/m2 twice daily PO, days 2 - 15

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Center	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Hoffmann-La Roche, Sanofi

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	conversion to resectability during downsizing therapy with IXO+A patients with initially unresectable liver-only metastases associated with colorectal cancer		after 8 IXO+A cycles	No
Secondary	Recurrence-free survival (RFS)		Every 2 cycles	No
Secondary	Progression-free survival (PFS)		Every 2 cycles	No
Secondary	Time to response (TTR)		Every 2 cycles	No
Secondary	Overall survival (OS)		Every 2 cycles	No
Secondary	Pathological complete response (pCR) rate		assessed post-operatory	No
Secondary	Overall response rate (ORR)		Every 2 cycles	No
Secondary	Number of participants with Adverse Events as a measure of Safety and Tolerability		Every 3 weeks	Yes
Secondary	Surgical safety (frequency of surgical complications)		assessed post-operatory	Yes
Secondary	Pathological changes in the non-tumoural liver following therapy with IXO+A		assessed post-operatory	Yes
Secondary	R0, R1, R2 resection rate after up to 8 cycles of downsizing therapy with IXO+A		assessed post-operatory	No