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Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

Phase 3
Completed
Conditions
Metastatic Cancer
Colorectal Cancer
Interventions
Procedure: laparotomy
Procedure: conventional surgery
Registration Number
NCT00002716
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective for metastatic colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of intrahepatic floxuridine, leucovorin, and dexamethasone with that of systemic fluorouracil and leucovorin in treating patients who have unresectable liver metastases from colorectal cancer.

Detailed Description

OBJECTIVES:

* Compare the efficacy, toxicity, and cost of hepatic artery infusion of floxuridine, leucovorin calcium (CF), and dexamethasone vs IV fluorouracil and IV CF after resection of primary disease in patients with hepatic metastases secondary to colorectal cancer.

* Compare the quality of life of patients treated with these regimens.

* Measure the level of thymidylate synthase present in liver metastases, and correlate these levels with objective response and survival in patients treated with these regimens.

* Assess the p53 mutations, and correlate findings with objective response and survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, percentage of liver involvement on CT scan or MRI (less than 30% vs 30% to under 70%), prior chemotherapy (none vs adjuvant chemotherapy comprising fluorouracil (5-FU) and leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV) completed at least 1 year before study vs adjuvant chemotherapy comprising 5-FU with or without LEV completed at least 6 months before study), and synchronous disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
135
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I - laparotomy + conventional surgery + chemotherapyleucovorin calciumPatients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm I - laparotomy + conventional surgery + chemotherapyconventional surgeryPatients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm II - conventional surgery + chemotherapyleucovorin calciumPatients receive CF IV and fluorouracil IV on days 1-5. Patients with unresected primary disease undergo resection within 3-4 weeks before initiation of chemotherapy. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm I - laparotomy + conventional surgery + chemotherapylaparotomyPatients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm II - conventional surgery + chemotherapyconventional surgeryPatients receive CF IV and fluorouracil IV on days 1-5. Patients with unresected primary disease undergo resection within 3-4 weeks before initiation of chemotherapy. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm I - laparotomy + conventional surgery + chemotherapydexamethasonePatients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm I - laparotomy + conventional surgery + chemotherapyfloxuridinePatients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Arm II - conventional surgery + chemotherapyfluorouracilPatients receive CF IV and fluorouracil IV on days 1-5. Patients with unresected primary disease undergo resection within 3-4 weeks before initiation of chemotherapy. Treatment for patients continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months. Patients are followed every 3 months.
Primary Outcome Measures
NameTimeMethod
Overall survivalUp to 5 years
Time to progressionUp to 5 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (14)

CCOP - Cedar Rapids Oncology Project

🇺🇸

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

🇺🇸

Des Moines, Iowa, United States

John Stoddard Cancer Center at Iowa Methodist Medical Center

🇺🇸

Des Moines, Iowa, United States

Iowa Lutheran Hospital

🇺🇸

Des Moines, Iowa, United States

Mercy Cancer Center at Mercy Medical Center-Des Moines

🇺🇸

Des Moines, Iowa, United States

MBCCOP - University of New Mexico HSC

🇺🇸

Albuquerque, New Mexico, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

🇺🇸

Green Bay, Wisconsin, United States

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Instituto de Enfermedades Neoplasicas

🇵🇪

Lima, Peru

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Midlands Cancer Center at Midlands Community Hospital

🇺🇸

Papillion, Nebraska, United States

MetroHealth Medical Center

🇺🇸

Cleveland, Ohio, United States

San Juan City Hospital

🇵🇷

San Juan, Puerto Rico

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