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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Metastatic Cancer

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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 SupportBethesda, Maryland  20892-1182