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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: floxuridine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Recruiting
      • Center for Cancer Care at Goshen General Hospital
      • Contact: Clinical Trials Office - Center for Cancer Care at Goshen Gene; Phone Number: 574-535-2858

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: oxaliplatin; Given IV; Drug: leucovorin calcium; Given IV; Drug: fluorouracil; Given IV
Experimental: 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.	Drug: leucovorin calcium; Given IV; Drug: fluorouracil; Given IV; Drug: irinotecan hydrochloride; Given IV
Experimental: FUDR; Patients receive floxuridine IV continuously on days 1-14.	Drug: floxuridine; Given IV

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: Goshen Health System
• Investigators: Study Chair: Kenneth L. Pennington, MD, Goshen Health System

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Anticipated): June 1, 2009

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 6, 2006
• First Posted (Estimate): December 7, 2006

Study Record Updates

• Last Update Posted (Estimate): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin; Floxuridine
• Other Study ID Numbers: CDR0000515900; CCCGHS-CHEMO-SIRT