Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Cancer and Leukemia Group B National Cancer Institute (NCI) Eastern Cooperative Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002716

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: adjuvant therapy Procedure: conventional surgery	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Dexamethasone Floxuridine Fluorouracil Leucovorin Citrovorum factor Dexamethasone acetate Doxiproct plus Leucovorin Calcium Dexamethasone Sodium Phosphate Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

January 1996

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.

Arm I: 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.

Arm II: 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 on both arms 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.

PROJECTED ACCRUAL: Approximately 340 patients (170 per arm) will be accrued for this study within approximately 4.5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
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

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

See Disease Characteristics
Bilirubin no greater than 2 times normal

Renal:

Not specified

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

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

Surgery:

See Disease Characteristics

Contacts and Locations

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
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316-2301
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
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
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
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

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Investigators

Study Chair:	Nancy E. Kemeny, MD	Memorial Sloan-Kettering Cancer Center
Study Chair:	Elin Ruth Sigurdson, MD	Fox Chase Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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. Epub 2006 Feb 27.

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.

Kemeny NE, Niedzwiecki D, Hollis DR, et al.: 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] Proceedings of the American Society of Clinical Oncology 22: A-1010, 252, 2003.

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.

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.

Study ID Numbers:	CDR0000064553, CALGB-9481, ECOG-C9481
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00002716 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

adenocarcinoma of the colon
adenocarcinoma of the rectum
liver metastases

Study placed in the following topic categories:

Antimetabolites
Anti-Inflammatory Agents
Dexamethasone
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Hormone Antagonists
Colonic Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Leucovorin
Antiemetics
Hormones
Rectal Diseases
Vitamins
Neoplasm Metastasis

Micronutrients
Dexamethasone acetate
Vitamin B Complex
Digestive System Neoplasms
Antineoplastic Agents, Hormonal
Floxuridine
Rectal Neoplasm
Adjuvants, Immunologic
Trace Elements
Folinic Acid
Intestinal Diseases
Immunosuppressive Agents
Glucocorticoids
Intestinal Neoplasms
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Dexamethasone
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Colonic Diseases
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Leucovorin
Antiemetics
Hormones
Rectal Diseases

Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Vitamins
Therapeutic Uses
Neoplasm Metastasis
Micronutrients
Dexamethasone acetate
Vitamin B Complex
Digestive System Neoplasms
Antineoplastic Agents, Hormonal
Floxuridine
Growth Substances
Gastrointestinal Agents
Intestinal Diseases

ClinicalTrials.gov processed this record on July 02, 2009