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
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Locations
- 4
- Primary Endpoint
- conversion to resectability during downsizing therapy with IXO+A patients with initially unresectable liver-only metastases associated with colorectal cancer
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
IXO+A
IXO regimen with Avastin
Intervention: irinotecan, capecitabine, oxaliplatin (IXO) and bevacizumab (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Recurrence-free survival (RFS)(Every 2 cycles)
- Progression-free survival (PFS)(Every 2 cycles)
- Time to response (TTR)(Every 2 cycles)
- Overall survival (OS)(Every 2 cycles)
- Pathological complete response (pCR) rate(assessed post-operatory)
- Overall response rate (ORR)(Every 2 cycles)
- Number of participants with Adverse Events as a measure of Safety and Tolerability(Every 3 weeks)
- Surgical safety (frequency of surgical complications)(assessed post-operatory)
- Pathological changes in the non-tumoural liver following therapy with IXO+A(assessed post-operatory)
- R0, R1, R2 resection rate after up to 8 cycles of downsizing therapy with IXO+A(assessed post-operatory)