IXO+A in mCRC With Liver-only Metastases

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
Hoffmann-La Roche
Sanofi
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01293942
First received: February 8, 2011
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: irinotecan, capecitabine, oxaliplatin (IXO) and bevacizumab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • conversion to resectability during downsizing therapy with IXO+A patients with initially unresectable liver-only metastases associated with colorectal cancer [ Time Frame: after 8 IXO+A cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recurrence-free survival (RFS) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Time to response (TTR) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Pathological complete response (pCR) rate [ Time Frame: assessed post-operatory ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Number of participants with Adverse Events as a measure of Safety and Tolerability [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
  • Surgical safety (frequency of surgical complications) [ Time Frame: assessed post-operatory ] [ Designated as safety issue: Yes ]
  • Pathological changes in the non-tumoural liver following therapy with IXO+A [ Time Frame: assessed post-operatory ] [ Designated as safety issue: Yes ]
  • R0, R1, R2 resection rate after up to 8 cycles of downsizing therapy with IXO+A [ Time Frame: assessed post-operatory ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: March 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IXO+A
IXO regimen with Avastin
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01293942

Locations
Canada, Ontario
The Ottawa Hospital Cancer Center
Ottawa, Ontario, Canada, K1H 8L6
University Health Network
Toronto, Ontario, Canada, M5T 2S8
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
McGill University Health Centre
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
Ottawa Hospital Research Institute
Hoffmann-La Roche
Sanofi
Investigators
Study Chair: Jean Maroun, MD The Ottawa Hospital Cancer Centre
  More Information

No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01293942     History of Changes
Other Study ID Numbers: OTT 10-01
Study First Received: February 8, 2011
Last Updated: June 4, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
unresectable liver-only metastases in colorectal cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Colorectal Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Irinotecan
Capecitabine
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014