Radiation Therapy and Fluorouracil Before Surgery in Treating Patients With Primary or Recurrent Bile Duct Cancer

A Phase II Study of Chronomodulated Preoperative Infusional Chemoradiation for Biliary Tract Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase II trial to study the effectiveness of combining radiation therapy with fluorouracil before surgery in treating patients who have primary or recurrent bile duct cancer.

Study Overview

• Status: Terminated
• Conditions: Liver Cancer; Extrahepatic Bile Duct Cancer
• Intervention / Treatment: Drug: fluorouracil; Radiation: radiation therapy; Procedure: conventional surgery

Detailed Description

OBJECTIVES:

• Determine the pathologic response rate in patients with primary or recurrent biliary duct carcinoma treated with neoadjuvant radiotherapy and fluorouracil followed by surgical resection.
• Determine the tumor response, morbidity, failure patterns (locoregional vs distant), and survival in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients undergo radiotherapy once daily five days a week for 5.5 weeks. Patients receive fluorouracil IV over 12 hours each day radiotherapy is administered. Four to six weeks after completion of chemoradiotherapy, patients undergo surgical resection. Patients with residual disease after resection may undergo boost radiotherapy.

Patients are followed every 12 weeks until disease progression and then every 16 weeks after disease progression.

PROJECTED ACCRUAL: A total of 20-47 patients will be accrued for this study within 2.5 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Haine Saint Paul, Belgium, 7100
    • Hôpital de Jolimont
  • Liege, Belgium, B 4000
    • Les Cliniques Saint-Joseph ASBL
• France
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges
  • Paris, France, 75674
    • Hopital Cochin
  • Villejuif, France, 94804
    • Hôpital Paul Brousse
• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary or recurrent biliary duct carcinoma from the proximal, middle, or distal bile ducts
• Measurable or evaluable disease that is considered resectable

• No distant metastases

  • No non-contiguous liver metastases
  • Resectable extension into adjacent liver allowed
  • No metastasis to peritoneal cavity
  • No Bismuth type 4 lesion or metastasis to celiac axis or para-aortic lymph nodes
• No tumor encasement of portal vein or hepatic artery
• No gross ascites

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• No cirrhosis
• No active cholangitis
• No fever or signs of infection in biliary drainage system
• Measurement of C-reactive protein optimal
• Bilirubin less than 3 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Other:

• Not pregnant or nursing
• Fertile patients must use effective barrier contraception during and for 3 months after study
• No weight loss greater than 20% ideal body weight
• No active duodenal or gastric ulcers
• No other prior or concurrent primary malignancy except adequately treated carcinoma in situ of the cervix or basal cell carcinoma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Tyvin A. Rich, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (Actual): July 1, 2003

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 16, 2012
• Last Update Submitted That Met QC Criteria: July 13, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: recurrent adult primary liver cancer; recurrent extrahepatic bile duct cancer; localized resectable adult primary liver cancer; localized extrahepatic bile duct cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Liver Neoplasms; Bile Duct Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: EORTC-05991