Conversion From Unresectable To Resectable Metastatic Colorectal Cancer.

Study Overview
=================
Brief Summary
-----------------
Most patients with mCRC are treated with palliative chemotherapy and only a small number of patients with limited metastatic disease achieve long-term remission following metastasectomy. There is a growing need for more effective treatment in patients with liver-only mCRC to improve the rate of curative resection without compromising QOL.The current study is informed by our patient's needs. It aims to evaluate the rate of conversion therapy in patients with unresectable liver-only mCRC using the combination of FOLFOXIRI and bevacizumab and to assess the association between an early FDG-PT/CT response and other clinical and pathological biomarkers and hepatic metastasectomy.

Detailed Description
-----------------
Colorectal cancer is the second leading cause of cancer-related death in North America. Patients with metastatic colorectal cancer generally have limited life expectancy, however, a small number of patients with liver-only metastases could potentially be cured following surgical resection of metastases. Patients and their family strongly feel that there is an unmet need for a more effective treatment in metastatic colorectal cancer to improve disease response rate and thereby curative surgery. Recent evidence suggest that a triplet chemotherapy regimen, FOLFOXIRI plus bevacizumab has been associated with higher response rates. The CONVERSION trial will evaluate the rate of conversion from unresectable to resectable liver metastases in patients with liver-only metastatic colorectal cancer treated with FOLFOXIRI-bevacizumab. Furthermore, this study will assess disease control rate, survival, quality of life and association between various biomarkers including an early FDG-PET/CT response and curative surgery. Thirty-two eligible patients will be recruited at the two major cancer centers in Saskatchewan. Patients will receive FOLFOXIRI-bevacizumab every two weeks for a total of 12 cycles and will undergo periodic imaging studies. The resectability of liver metastases will be assessed by a multidisciplinary team comprised of surgeons, radiologists, and oncologists. This study will be helpful to establish a standard chemotherapy regimen for patients with liver-only metastatic colorectal cancer and to determine the role of FDG-PET/CT scan and other biomarkers in predicting curative surgery. Complete resection of metastases will allow such patients to discontinue chemotherapy and live a normal life.

Official Title
-----------------
Conversion From Unresectable To Resectable Liver Metastases In Patients With Liver-Only Metastatic Colorectal Cancer Treated With FOLFOXIRI Plus Bevacizumab. The Conversion Trial.

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: FOLFOXIRI and Bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients, aged between 18 and 70 years with histologically proven adenocarcinoma or poorly differentiated carcinoma of the colon and rectum with unresectable liver-only metastases and no extra-hepatic disease. World Health Organization (WHO) performance status of 0-1. No previous chemotherapy for advanced disease. Adequate functioning of the bone marrow, liver, and kidneys. Exclusion Criteria: Breastfeeding or pregnancy. An active second primary cancer with the exception of squamous cell carcinoma of the skin or an in situ cancer. Severe or uncompensated concomitant medical conditions.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm<br>FOLFOXIRI and Bevacizumab | Drug: FOLFOXIRI and Bevacizumab<br>* Every 2 week for a total of 12 cycles<br>* Other names: 5FU, leucovorin, oxaliplatin, irinotecan and bevacizumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of liver metastasectomy | Conversion From Unresectable To Resectable Liver Metastases | Up to 3 years from the date of enrolment into the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Based on RECIST criteria | Up to 12 weeks of last cycle of FOLFOXIRI from the date of enrolment till the date of maximum response | 
| 30 days rates of Grade III and IV toxicity | As per National Cancer Institute Common Toxicity Criteria | Up to 30 days of last cycle of FOLFOXIRI from the date of enrolment till the date of toxicity | 
| The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) | Quality of life questionnaire related to cancer and its treatment | up to 3 years from the date of enrolment or till the progression of the disease | 
| The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer Module (QLQ-CR29) | Quality of life questionnaire specifically related to colorectal cancer | up to 3 years from the date of enrolment or till the progression of the disease | 
| The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Liver Metastases Module (LMC21) | Quality of life questionnaire specifically related to liver metastases | up to 3 years from the date of enrolment or till the progression of the disease | 
| Early-PET scan response | change in FDG-uptake between baseline and after 4 cycles of chemotherapy and it correlation with rate of metastasectomy | From the date of enrolment till 8 weeks after four cycles of FOLOXIRI and bevacizumab | 
| Progression-free survival | progression following FOLOXIRI and bevacizumab | up to 5 years from the time of enrolment till disease progression or last follow up visit | 
| Overall survival | all cause mortality | up to 5 years from the time of enrolment till mortality or last follow up visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastatic colorectal cancer, Conversion therapy, Liver Metastasectomy