AzTrials
AzTrials

Colorectal CancerPhase 3NCT00002716

Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

A Phase 3 study testing dexamethasone, floxuridine and fluorouracil in people with Colorectal Cancer and Metastatic Cancer, run by Alliance for Clinical Trials in Oncology at 14 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer, Metastatic Cancer
What is being tested?
dexamethasone, floxuridine and fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
14 sitesin 4 countries
Study dates
Jan 1996to Aug 2006
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

14 sites in 4 countries.

14 sites in 4 countries

United States11 sites

  • MBCCOP - University of New Mexico HSC

    Albuquerque, New Mexico, 87131

  • CCOP - Cedar Rapids Oncology Project

    Cedar Rapids, Iowa, 52403-1206

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • CCOP - Iowa Oncology Research Association

    Des Moines, Iowa, 50309-1016

  • John Stoddard Cancer Center at Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Mercy Cancer Center at Mercy Medical Center-Des Moines

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316-2301

  • CCOP - St. Vincent Hospital Cancer Center, Green Bay

    Green Bay, Wisconsin, 54307-3453

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Midlands Cancer Center at Midlands Community Hospital

    Papillion, Nebraska, 68128-4157

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

Other trials in United States

Australia1 site

  • Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

Peru1 site

  • Instituto de Enfermedades Neoplasicas

    Lima, 34

Other trials in Peru

Puerto Rico1 site

  • San Juan City Hospital

    San Juan, 00936-7344

Other trials in Puerto Rico

About this study

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

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.

Read the 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.

Being tested
dexamethasone, floxuridine, fluorouracil, leucovorin calcium, laparotomy
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, liver metastases
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00002716
Study groupRoleWhat they receive
Arm I - laparotomy + conventional surgery + chemotherapyExperimentalPatients 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.
Receives: Drug: dexamethasone; Drug: floxuridine; Drug: leucovorin calcium; Procedure: laparotomy; Procedure: conventional surgery
Arm II - conventional surgery + chemotherapyExperimentalPatients 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.
Receives: Drug: fluorouracil; Drug: leucovorin calcium; Procedure: conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Measured: Up to 5 years

  2. Time to progression

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJan 1996
  3. Primary completionMar 2006
  4. Study completionAug 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00002716
Sponsor's protocol ID
CALGB-9481
Other IDs
U10CA031946, CDR0000064553
Status last verified
Jul 2016
First submitted
1 Nov 1999
Last updated
13 Jul 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 16505413

  • 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.

  • 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.

    PubMed 12782596

  • 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.

    PubMed 11913730

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dexamethasone, floxuridine and fluorouracil in people with Colorectal Cancer and Metastatic Cancer, run by Alliance for Clinical Trials in Oncology at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Australia, Peru, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00002716, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in