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Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00002716
First received: November 1, 1999
Last updated: July 12, 2016
Last verified: July 2016
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: dexamethasone
Drug: floxuridine
Drug: fluorouracil
Drug: leucovorin calcium
Procedure: laparotomy
Procedure: conventional surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE III STUDY OF HEPATIC ARTERY FLOXURIDINE (FUDR), LEUCOVORIN (LV), AND DEXAMETHASONE (DEX) VERSUS SYSTEMIC 5-FLUOROURACIL (5-FU) AND LEUCOVORIN (LV) AS TREATMENT FOR HEPATIC METASTASES FROM COLORECTAL CANCER

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 135
Study Start Date: January 1996
Study Completion Date: August 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I - laparotomy + conventional surgery + chemotherapy

Patients 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.

Drug: dexamethasone Drug: floxuridine Drug: leucovorin calcium Procedure: laparotomy Procedure: conventional surgery
Experimental: Arm II - conventional surgery + chemotherapy

Patients 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.

Drug: fluorouracil Drug: leucovorin calcium Procedure: conventional surgery

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Unresectable liver metastases secondary to colorectal cancer

    • Less than 70% liver involvement on CT scan or MRI
    • Liver biopsy required before study unless 1 of the following conditions are met:

      • Carcinoembryonic antigen greater than 30
      • 5 or more liver metastases visible on CT scan or MRI
      • Greater than 50% to under 70% liver involvement on CT scan or MRI
  • Histologically proven primary colorectal cancer that is resected or appears resectable on CT scan and physical exam

    • Documentation of previously resected primaries must be based on pathologic results of the resected tumor
    • Histological documentation of synchronous disease must be based on 1 of the following:

      • Biopsy of primary colorectal tumor before study
      • Suspicious lesion on barium enema, colonoscopy, or sigmoidoscopy, and a liver biopsy positive for adenocarcinoma consistent with the primary colorectal tumor
  • Measurable disease

    • Clearly defined liver mass measuring at least 2 cm or at least 3 liver masses on CT scan or MRI
  • No evidence of extrahepatic disease on CT scan and physical exam
  • No portal vein occlusion or ascites

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Hepatic:

  • Bilirubin no greater than 2 times normal

Other:

  • No other malignancy within the past 5 years except inactive nonmelanomatous skin cancer, carcinoma in situ of the cervix, or grade 1 bladder cancer
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

Chemotherapy:

  • At least 1 year since prior adjuvant chemotherapy comprising fluorouracil (5-FU) and leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV)
  • At least 6 months since prior adjuvant chemotherapy comprising 5-FU with or without LEV
  • No other prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy except for nondisease-related conditions, e.g.:

    • Steroids for adrenal failure
    • Insulin for diabetes
    • Intermittent dexamethasone as an antiemetic

Radiotherapy:

  • No prior radiotherapy to the liver
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002716

Locations
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Mercy Cancer Center at Mercy Medical Center-Des Moines
Des Moines, Iowa, United States, 50314
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316-2301
United States, Nebraska
Midlands Cancer Center at Midlands Community Hospital
Papillion, Nebraska, United States, 68128-4157
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54307-3453
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Peru
Instituto de Enfermedades Neoplasicas
Lima, Peru, 34
Puerto Rico
San Juan City Hospital
San Juan, Puerto Rico, 00936-7344
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Nancy E. Kemeny, MD Memorial Sloan Kettering Cancer Center
  More Information

Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00002716     History of Changes
Other Study ID Numbers: CALGB-9481  U10CA031946  CDR0000064553 
Study First Received: November 1, 1999
Last Updated: July 12, 2016
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
liver metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Fluorouracil
Floxuridine
BB 1101
Levoleucovorin
Leucovorin
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on September 30, 2016