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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00002716




Registration number
NCT00002716
Ethics application status
Date submitted
1/11/1999
Date registered
27/01/2003
Date last updated
13/07/2016

Titles & IDs
Public title
Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer
Scientific 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
Secondary ID [1] 0 0
U10CA031946
Secondary ID [2] 0 0
CALGB-9481
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Metastatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.

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.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Up to 5 years
Primary outcome [2] 0 0
Time to progression
Timepoint [2] 0 0
Up to 5 years

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/1996
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2006
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Iowa
Country [2] 0 0
United States of America
State/province [2] 0 0
Nebraska
Country [3] 0 0
United States of America
State/province [3] 0 0
New Mexico
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Peru
State/province [7] 0 0
Lima
Country [8] 0 0
Puerto Rico
State/province [8] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Alliance for Clinical Trials in Oncology
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00002716
Trial related presentations / 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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Nancy E. Kemeny, MD
Address 0 0
Memorial Sloan Kettering Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00002716