Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

NCT00002716 | Completed Phase 3

• 3 other identifiers: CALGB-9481U10CA031946CDR0000064553
• Study Type: interventional
• Target: 135
• Locations: 4 countries
• Sites: 14

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.

Conditions

Colorectal Cancer; Metastatic Cancer

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

Outcome Measures

Primary Outcomes (2)

• Overall survival

  Up to 5 years

• Time to progression

  Up to 5 years

Study Arms (2)

Arm I - laparotomy + conventional surgery + chemotherapy

EXPERIMENTAL

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.

Drug: dexamethasone; Drug: floxuridine; Drug: leucovorin calcium; Procedure: laparotomy; Procedure: conventional surgery

Arm II - conventional surgery + chemotherapy

EXPERIMENTAL

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.

Drug: fluorouracil; Drug: leucovorin calcium; Procedure: conventional surgery

Interventions

dexamethasone DRUG

Arm I - laparotomy + conventional surgery + chemotherapy

floxuridine DRUG

Arm I - laparotomy + conventional surgery + chemotherapy

fluorouracil DRUG

Arm II - conventional surgery + chemotherapy

leucovorin calcium DRUG

Arm I - laparotomy + conventional surgery + chemotherapy; Arm II - conventional surgery + chemotherapy

laparotomy PROCEDURE

Arm I - laparotomy + conventional surgery + chemotherapy

conventional surgery PROCEDURE

Arm I - laparotomy + conventional surgery + chemotherapy; Arm II - conventional surgery + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (14)

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, 52403-1206, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309-1016, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Mercy Cancer Center at Mercy Medical Center-Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316-2301, United States

Location

Midlands Cancer Center at Midlands Community Hospital

Papillion, Nebraska, 68128-4157, United States

Location

MBCCOP - University of New Mexico HSC

Albuquerque, New Mexico, 87131, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, 54307-3453, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Instituto de Enfermedades Neoplasicas

Lima, 34, Peru

Location

San Juan City Hospital

San Juan, 00936-7344, Puerto Rico

Location

Related Publications (4)

• 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 RESULT

• 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.

  RESULT

• 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 RESULT

• 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 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

Dexamethasone; Floxuridine; Fluorouracil; Leucovorin; Laparotomy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Surgical Procedures, Operative

Study Officials

• Nancy E. Kemeny, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: January 1, 1996
• Primary Completion: March 1, 2006
• Study Completion: August 1, 2006
• Last Updated: July 13, 2016

Record last verified: 2016-07

Locations

AU (1); PR (1); PE (1); US (11)