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NCT00002716 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-07-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: dexamethasone
    2. Drug: floxuridine
    3. Drug: leucovorin calcium
    4. Procedure: laparotomy
    5. Procedure: conventional surgery
    label
    Arm I - laparotomy + conventional surgery + chemotherapy
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Drug: fluorouracil
    2. Drug: leucovorin calcium
    3. Procedure: conventional surgery
    label
    Arm II - conventional surgery + chemotherapy
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I - laparotomy + conventional surgery + chemotherapy
    name
    dexamethasone
    type
    DRUG
  2. arm Group Labels
    1. Arm I - laparotomy + conventional surgery + chemotherapy
    name
    floxuridine
    type
    DRUG
  3. arm Group Labels
    1. Arm II - conventional surgery + chemotherapy
    name
    fluorouracil
    type
    DRUG
  4. arm Group Labels
    1. Arm I - laparotomy + conventional surgery + chemotherapy
    2. Arm II - conventional surgery + chemotherapy
    name
    leucovorin calcium
    type
    DRUG
  5. arm Group Labels
    1. Arm I - laparotomy + conventional surgery + chemotherapy
    name
    laparotomy
    type
    PROCEDURE
  6. arm Group Labels
    1. Arm I - laparotomy + conventional surgery + chemotherapy
    2. Arm II - conventional surgery + chemotherapy
    name
    conventional surgery
    type
    PROCEDURE
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
135
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Overall survival
    time Frame
    Up to 5 years
  2. measure
    Time to progression
    time Frame
    Up to 5 years
Full study description
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.
Source references
references
  1. citation
    Kemeny NE, Niedzwiecki D, Hollis DR, Lenz HJ, Warren RS, Naughton MJ, Weeks JC, Sigurdson ER, Herndon JE 2nd, Zhang C, Mayer RJ. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol. 2006 Mar 20;24(9):1395-403. doi: 10.1200/JCO.2005.03.8166. Epub 2006 Feb 27.
    pmid
    16505413
    type
    RESULT
  2. citation
    Kemeny NE, Niedzwiecki D, Hollis DR, et al.: Final analysis of hepatic arterial infusion (HAI) versus systemic therapy for hepatic metastases from colorectal cancer: a CALGB randomized trial of efficacy, quality of life (QOL), cost effectiveness, and molecular markers. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-183, 2005.
    type
    RESULT
  3. citation
    Mandola MV, Stoehlmacher J, Muller-Weeks S, Cesarone G, Yu MC, Lenz HJ, Ladner RD. A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res. 2003 Jun 1;63(11):2898-904.
    pmid
    12782596
    type
    RESULT
  4. citation
    Pullarkat ST, Stoehlmacher J, Ghaderi V, Xiong YP, Ingles SA, Sherrod A, Warren R, Tsao-Wei D, Groshen S, Lenz HJ. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J. 2001;1(1):65-70. doi: 10.1038/sj.tpj.6500012.
    pmid
    11913730
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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        sy regarding the efficacy of regional chemotherapy was the basis of a large, multicenter, phase III trial (<a href="/clinicaltrials/NCT00002716">Leuk-9481</a> [NCT00002716]) of hepatic arterial infusion versus systemic chemotherapy. The use of combination intra-arterial chemotherapy with hepatic radiation therapy, especially emp
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      source update dates
      1. context
        Updated: February 12, 2025
        datetime
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        display
        February 12, 2025

    Preserved source evidence · Independent clinical review pending · Not medical advice