Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002716
• Other study ID #: CALGB-9481
• Secondary ID: U10CA031946CDR00
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: July 12, 2016
• Start date: January 1996
• Est. completion date: August 2006

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: August 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• dexamethasone

• floxuridine

• fluorouracil

• leucovorin calcium

Procedure:
• laparotomy

• conventional surgery

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales
Peru	Instituto de Enfermedades Neoplasicas	Lima
Puerto Rico	San Juan City Hospital	San Juan
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center-Des Moines	Des Moines	Iowa
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Midlands Cancer Center at Midlands Community Hospital	Papillion	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Peru,  Puerto Rico, 

References & Publications (4)

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 mole

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 efficac — View 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		Up to 5 years	No
Primary	Time to progression		Up to 5 years	No