Chemotherapy and Internal Radiation in Treating Patients With Colorectal Cancer That Has Spread to the Liver

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving chemotherapy together with internal radiation may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving chemotherapy together with internal radiation works in treating patients with colorectal cancer that has spread to the liver.

Detailed Description
-----------------
OBJECTIVES: Primary Evaluate the tumor response, as measured by total tumor mass, carcinoembryonic antigen (CEA) level, measurable tumor volume by CT scan, and metabolic response by positron emission tomography (PET) scan, in patients with colorectal cancer metastatic to the liver undergoing chemotherapy and selective internal radiation therapy (SIRT) comprising yttrium Y 90 resin microspheres. Evaluate the hepatic toxicity of this regimen, as measured by ALT, alkaline phosphatase, and bilirubin levels, in these patients. Secondary Evaluate the therapeutic efficacy of this regimen, using time to in-liver disease progression as an end point, in these patients. Evaluate the therapeutic efficacy of this regimen, using down-staging to resectability as an end point, in these patients. OUTLINE: This is a multicenter study. Patients receive 1 of the following chemotherapy regimens: FOLFOX6: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continously over 46 hours beginning on day 1. FOLFIRI: Patients receive irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. FUDR: Patients receive floxuridine IV continuously on days 1-14. In all chemotherapy regimens, treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo selective internal radiation therapy (SIRT) comprising yttrium Y 90 resin microspheres on day 2 of chemotherapy course 1 (for patients receiving FOLFOX6 or FOLFIRI chemotherapy regimens) or on day 1, 2, 3, 4, or 5 of course 1 (for patients receiving FUDR chemotherapy regimen). SIRT may repeat in week 10 or 12. In week 18, patients may undergo surgery if down-staging has occurred or they may receive more chemotherapy. After completion of study therapy, patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
-----------------
A Phase II Multi-Institutional Efficacy and Safety Study of Chemotherapy With Selective Internal Radiation Treatment Using Y-90 Microspheres (CHEMO-SIRT) in Patients With Colorectal Cancer Liver Metastasis

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

Intervention / Treatment
-----------------
* Drug: floxuridine
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed colorectal cancer* meeting 1 of the following criteria: Metachronous metastasis after resection of Dukes A-C (i.e., stage I-III) primary colon cancer with or without adjuvant chemotherapy Metachronous metastasis after resection of primary rectal cancer with neoadjuvant or adjuvant chemotherapy Synchronous metastatic liver disease with symptomatic or asymptomatic primary colorectal cancer NOTE: *If the patient has a second malignancy with liver metastasis potential, histologic or cytologic confirmation of the liver lesions may be performed as clinically indicated Liver-only or liver-predominant disease with any of the following: Unresected primary disease Limited bone or lung disease Potentially resectable nodal disease Anastomotic disease No active CNS metastasis or diffuse peritoneal metastasis No hepatic metastases from a second malignancy No predominant extrahepatic disease PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 3 months Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL WBC ≥ 1,500/mm^3 Creatinine ≤ 2 mg/dL Bilirubin ≤ 2 mg/dL (without extrahepatic biliary obstruction) Albumin > 2 g/dL INR < 1.5 (without anticoagulation) Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior external-beam radiotherapy to the liver Concurrent targeted therapy agents (e.g., bevacizumab or cetuximab) allowed

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFOX6<br>Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continously over 46 hours beginning on day 1. | Drug: fluorouracil<br>* Given IV<br>Drug: leucovorin calcium<br>* Given IV<br>Drug: oxaliplatin<br>* Given IV<br>|
| Experimental: FOLFIRI<br>Patients receive irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. | Drug: fluorouracil<br>* Given IV<br>Drug: irinotecan hydrochloride<br>* Given IV<br>Drug: leucovorin calcium<br>* Given IV<br>|
| Experimental: FUDR<br>Patients receive floxuridine IV continuously on days 1-14. | Drug: floxuridine<br>* Given IV<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response as measured by carcinoembryonic antigen (CEA) level, RECIST criteria, and positron emission tomography (PET) scan |  |  | 
| Hepatic toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic efficacy based on time from selective internal radiation therapy (SIRT) to in-liver disease progression |  |  | 
| Therapeutic efficacy based on the proportion of patients who achieve down-staging among all chemo-SIRT treated patients |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV colon cancer, stage IV rectal cancer, liver metastases, recurrent colon cancer, recurrent rectal cancer