Floxuridine, Dexamethasone, and Irinotecan After Surgery in Treating Patients With Liver Metastases From Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00003753
First received: November 1, 1999
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as floxuridine, dexamethasone, and irinotecan, use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of irinotecan combined with hepatic arterial infusion with floxuridine and dexamethasone after surgery in treating patients who have liver metastases from colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: dexamethasone
Drug: floxuridine
Drug: irinotecan hydrochloride
Procedure: adjuvant therapy
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Study of Hepatic Arterial Therapy Via Pump (Protocol D97-063) With Floxuridine (FUDR) and Dexamethasone (DEX) in Combination With Intravenous Irinotecan as Adjuvant Treatment After Resection of Hepatic Metastases From Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Study Start Date: September 1998
Study Completion Date: April 2004
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of hepatic arterial infusion of floxuridine (FUDR) and dexamethasone given via an implanted pump in combination with weekly intravenous irinotecan as adjuvant treatment after resection of hepatic metastases in patients with hepatic metastases from colorectal cancer. (The MTDs of irinotecan and floxuridine have been reached as of 10/15/03; phase I closed to accrual as of 10/15/03.)
  • Determine the efficacy of this combination chemotherapy after liver resection, in terms of 2-year survival and 2-year recurrence rates, in these patients.
  • Determine the pharmacokinetic effects of intrahepatic FUDR and liver resection on the metabolism of irinotecan to its active metabolite, SN-38 in these patients.
  • Determine the safety and efficacy of the pump used in delivering intra-arterial chemotherapy to the liver in these patients.

OUTLINE: This is a dose-escalation* study of floxuridine and irinotecan.

Patients undergo hepatic resection and pump placement into the abdomen. About 4 weeks after surgery, patients receive irinotecan IV over 30 minutes on days 1 and 15. Patients also receive floxuridine and dexamethasone intra-arterially via an implanted pump continuously on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity or disease progression.

Sequential dose escalation of irinotecan is followed by sequential dose escalation of floxuridine. Cohorts of 3-6 patients receive escalating doses of irinotecan and floxuridine until the maximum tolerated doses (MTDs) are determined. The MTD* (phase II dose) is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

NOTE: *The MTDs of irinotecan and floxuridine have been reached as of 10/15/03; phase I closed to accrual as of 10/15/03

Patients are followed every 3 months for 2 years, every 4 months for 2-4 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 2-24 patients will be accrued for the phase I portion of this study within 1 year (phase I closed to accrual as of 10/15/03). A total of 50 additional patients will be accrued for this study at the phase II dose level.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal adenocarcinoma
  • Primary colorectal tumor must have been previously resected
  • Potentially completely resectable hepatic metastases (or removable by cryoresection) without current evidence of other metastatic disease
  • No extrahepatic sites of disease
  • No ascites or hepatic encephalopathy

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • At least 4 weeks since prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy to the liver
  • At least 4 weeks since prior radiotherapy to the pelvis

Surgery:

  • See Disease Characteristics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003753

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Nancy E. Kemeny, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00003753     History of Changes
Other Study ID Numbers: 98-072, CDR0000066876, MSKCC-98072A(9), NCI-H99-0024
Study First Received: November 1, 1999
Last Updated: June 20, 2013
Health Authority: United States: Federal Government

Keywords provided by Memorial Sloan-Kettering Cancer Center:
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
liver metastases
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Irinotecan
Floxuridine
Camptothecin
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 26, 2014