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Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002716
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 13, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date July 13, 2016
Study Start Date  ICMJE January 1996
Actual Primary Completion Date March 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2015)
  • Overall survival [ Time Frame: Up to 5 years ]
  • Time to progression [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Metastatic Cancer
Intervention  ICMJE
  • Drug: dexamethasone
  • Drug: floxuridine
  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Procedure: laparotomy
  • Procedure: conventional surgery
Study Arms  ICMJE
  • 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.

    Interventions:
    • 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.

    Interventions:
    • Drug: fluorouracil
    • Drug: leucovorin calcium
    • Procedure: conventional surgery
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 7, 2015)
135
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 2006
Actual Primary Completion Date March 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Peru,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00002716
Other Study ID Numbers  ICMJE CALGB-9481
U10CA031946 ( U.S. NIH Grant/Contract )
CDR0000064553 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Nancy E. Kemeny, MD Memorial Sloan Kettering Cancer Center
PRS Account Alliance for Clinical Trials in Oncology
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP