IXO+A in mCRC With Liver-only Metastases

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: irinotecan, capecitabine, oxaliplatin (IXO) and bevacizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IXO+A<br>IXO regimen with Avastin | Drug: irinotecan, capecitabine, oxaliplatin (IXO) and bevacizumab<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unresectable liver-only metastases in colorectal cancer