FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
This study is a randomized, multi-center study that will compare the efficacy and safety of selective internal radiation therapy (SIRT) using SIR-Spheres microspheres plus a standard chemotherapy regimen of FOLFOX6m versus FOLFOX6m alone as first-line therapy in patients with non-resectable liver metastases from primary colorectal carcinoma. Treatment with the biologic agent bevacizumab, if part of the standard of care at participating institutions, is allowed within this study at the discretion of the Investigator.

Official Title
-----------------
Assessment of Overall Survival of FOLFOX6m Plus SIR-Spheres Microspheres Versus FOLFOX6m Alone as First-line Treatment in Patients With Non-resectable Liver Metastases From Primary Colorectal Carcinoma in a Randomised Clinical Study

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

Intervention / Treatment
-----------------
* Drug: FOLFOX6m
* Device: SIR-Spheres microspheres


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older Willing and able to provide written informed consent Unequivocal and measurable CT evidence of liver metastases which are not treatable by surgical resection or local ablation Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (Lung: 5 lesions total, < 1 cm, or 1 single lesion of up to 1.7 cm; Lymph nodules in one single anatomic area (pelvis, abdomen or chest): any number, < 2 cm) All imaging evidence used as part of the screening process must be within 28 days Suitable for either treatment regimen WHO performance status 0-1 Adequate hematological, renal and hepatic function Life expectancy of at least 3 months without any active treatment Exclusion Criteria: Evidence of ascites, cirrhosis, portal hypertension, main portal or venous involvement or thrombosis as determined by clinical or radiologic assessment Previous radiotherapy delivered to the liver Non-malignant disease that would render the patient unsuitable for treatment according to the protocol Peripheral neuropathy > grade 2 (NCI-CTC) Dose-limiting toxicity associated with previous adjuvant 5-FU or oxaliplatin chemotherapy Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is permitted provided that it was completed more than 6 months before entry into the study Pregnant or breast feeding Concurrent or prior history of cancer other than adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix Allergy to contrast media that would preclude angiography of the hepatic arteries

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. | Drug: FOLFOX6m<br> <br> |
| Experimental: Experimental Arm<br>Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. | Drug: FOLFOX6m<br> <br> Device: SIR-Spheres microspheres<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as the time interval between the date of randomization and the date of death from any cause. | From date of randomization until the date of death from any cause assessed up 3 yrs 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | PFS defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as an increase in the sum of the longest diameters of ≥ 20% and an absolute increase in the sum of the longest diameters of ≥ 5 mm, or the appearance of a new lesion. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years 8 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colon, rectum, metastatic colorectal cancer, liver metastases