A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver
18 Years
N/A
Both
Colorectal Cancer, Metastatic Cancer
Trial Information
A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver
OBJECTIVES:
- Compare the disease-free and overall survival of patients with unresectable colorectal
cancer metastatic to the liver treated with regional and systemic chemotherapy with or
without isolated hepatic perfusion with melphalan.
- Compare the response rate and duration of response in patients treated with these
regimens.
- Compare the patterns of recurrence (liver vs systemic) in patients treated with these
regimens.
- Compare the health-related quality of life (QOL) of patients treated with these
regimens.
- Determine whether baseline QOL correlates with length of survival of patients treated
with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy
for liver metastasis (yes vs no) and percentage of hepatic replacement (less than 25% vs at
least 25%). All patients undergo laparotomy to determine final eligibility. Eligible
patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo hyperthermic isolated hepatic perfusion with melphalan over 60
minutes. Patients then undergo placement of an intrahepatic pump or port. At 6 weeks
post hepatic perfusion, patients receive systemic chemotherapy comprising irinotecan IV
over 90 minutes on day 1 followed by fluorouracil IV over 15 minutes and leucovorin
calcium (CF) IV over 15 minutes on days 1-3. Patients receive local chemotherapy
comprising floxuridine (FUDR) and CF by hepatic arterial infusion (HAI) continuously on
days 14-28.
- Arm II: Patients undergo placement of an intrahepatic pump or port at laparotomy. At 7
days post laparotomy, patients receive FUDR and CF by HAI continuously for 14 days.
Beginning 2 weeks after completion of HAI, patients receive systemic and local
chemotherapy as in arm I.
Treatment with combined systemic and local chemotherapy repeats every 35 days for a maximum
of 6 courses. Treatment with local chemotherapy alone repeats every 28 days for a maximum of
6 additional courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, postoperatively, every third course of
chemotherapy, every 3 months for 2 years, and then every 6 months thereafter.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 168 patients (84 per treatment arm) will be accrued for this
study within 54 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed metastatic colorectal cancer of the
parenchyma of the liver
- No evidence of extrahepatic disease (limited resectable extrahepatic disease
allowed)
- Unresectable liver metastasis, as defined by the following:
- More than 3 sites of disease
- Bilobar disease
- Tumor abutting major vascular or ductal structures
- Measurable disease
- No biopsy-proven cirrhosis or evidence of significant portal hypertension manifested
by ascites, esophageal varices, or collateral vessels around organs drained by the
portal venous system
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Platelet count greater than 100,000/mm^3
- Hematocrit greater than 27.0%
- WBC greater than 3,000/mm^3
Hepatic:
- Bilirubin less than 2.0 mg/dL
- PT no greater than 2 seconds over upper limit of normal
- Elevations in transaminases secondary to metastatic disease allowed
- No veno-occlusive disease
- No active chronic hepatitis
- Hepatitis B or C allowed provided there is no evidence of cirrhosis
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- No ischemic cardiac disease
- No prior congestive heart failure with LVEF less than 40%
Pulmonary:
- No chronic obstructive pulmonary disease or other chronic pulmonary disease with
pulmonary function test less than 50% of predicted
Other:
- No active infections
- Not pregnant or nursing
- Negative pregnancy test
- Weight greater than 30 kg
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior biologic therapy for disease and recovered
Chemotherapy:
- At least 4 weeks since prior chemotherapy for disease and recovered
- No prior intrahepatic artery infusion therapy with floxuridine
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 4 weeks since prior radiotherapy for disease and recovered
Surgery:
- Not specified
Other:
- No concurrent immunosuppressive drugs
- No concurrent chronic anticoagulants
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
H. Richard Alexander, MD, FACS
Investigator Role:
Study Chair
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Federal Government
Study ID:
010093
NCT ID:
NCT00020501
Start Date:
March 2001
Completion Date:
January 2005
Related Keywords:
- Colorectal Cancer
- Metastatic Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- liver metastases
- Colorectal Neoplasms
- Liver Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
