A Phase II Trial of Isolated Hepatic Perfusion (IHP) and Systemic FOLFOX4 for Subjects With Metastatic Unresectable Colorectal Cancers of the Liver With ≥ 40% Hepatic Tumor Burden


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Metastatic Cancer

Thank you

Trial Information

A Phase II Trial of Isolated Hepatic Perfusion (IHP) and Systemic FOLFOX4 for Subjects With Metastatic Unresectable Colorectal Cancers of the Liver With ≥ 40% Hepatic Tumor Burden


OBJECTIVES:

Primary

- Determine the response and duration of response in patients with previously untreated
unresectable liver metastases secondary to colorectal cancer treated with isolated
hepatic perfusion with melphalan followed by leucovorin calcium, oxaliplatin, and
fluorouracil.

Secondary

- Determine the patterns of recurrence (liver vs systemic) in patients treated with this
regimen.

- Determine progression-free and overall survival of patients treated with this regimen.

- Correlate health-related quality of life with length of survival of patients treated
with this regimen.

OUTLINE: Patients undergo exploratory laparotomy. Patients with evidence of carcinomatosis
not previously visualized on scans but found on surgical exploration are removed from the
study. All other patients then undergo isolated hepatic perfusion (IHP). Once IHP is
established, melphalan is administered intra-arterially over 3-5 minutes and then circulated
throughout the liver for 1 hour. Approximately 6-12 weeks later, patients receive systemic
chemotherapy comprising oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over
2 hours and fluorouracil IV continuously over 22 hours on days 1-2. Courses with systemic
chemotherapy repeat every 14 days for up to 1 year in the absence of disease progression or
unacceptable toxicity.

Quality of life is assessed at baseline, after laparotomy, after completion of systemic
chemotherapy, and then every 6 months thereafter.

After completion of study treatment, patients are followed every 3 months for 1 year, every
3-4 months for 2 years, and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2-3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed colorectal cancer

- Metastatic disease limited to the parenchyma of the liver

- No evidence of unresectable extrahepatic disease by preoperative radiology

- Limited extra-hepatic disease and dominant life-limiting liver disease
allowed provided extra-hepatic sites are treatable by local ablative
measures (e.g., surgical resection or external beam radiotherapy)

- At least 40% hepatic replacement by tumor by axial CT scan or MRI

- Unresectable liver metastases, defined by 1 of the following:

- More than 3 sites of disease in the liver

- Bilobar disease

- Tumor abutting major vascular or ductal structures

- Measurable disease

- Previously untreated disease

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Hematocrit > 27.0%

- WBC > 3,000/mm^3

- Platelet count > 100,000/mm^3

Hepatic

- Bilirubin < 2.0 mg/dL

- PT < 2 seconds above upper limit of normal

- Elevated transaminase levels allowed if due to liver metastases

- No cirrhosis by biopsy

- No significant portal hypertension as manifested by any of the following:

- Ascites

- Esophageal varices by endoscopy

- Significant collateral vessels around the organs drained by the portal venous
system by radiography

- No chronic active hepatitis

- Hepatitis B and C surface antigen negative

- No history of veno-occlusive disease

Renal

- Creatinine ≤ 1.5 mg/dL OR

- Creatinine clearance > 60 mL/min

Cardiovascular

- No ischemic cardiac disease

- No history of congestive heart failure

- LVEF > 40% by echocardiogram or stress thallium scan (for patients with cardiac
disease)

Pulmonary

- No chronic obstructive pulmonary disease or other chronic pulmonary disease

- Pulmonary function tests ≥ 50% of predicted (for patients with pulmonary disease)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Weight > 30 kg

- No active infection

- No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Prior adjuvant chemotherapy (including leucovorin calcium, oxaliplatin, and
fluorouracil) allowed provided it was administered > 6 months before liver metastases
were diagnosed

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy for this malignancy and recovered

Surgery

- Not specified

Other

- No concurrent chronic anticoagulation therapy

- No concurrent immunosuppressive drugs

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response and duration of response

Safety Issue:

No

Principal Investigator

H. Richard Alexander, MD, FACS

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Surgery Branch

Authority:

United States: Federal Government

Study ID:

CDR0000409754

NCT ID:

NCT00103298

Start Date:

December 2004

Completion Date:

July 2006

Related Keywords:

  • Colorectal Cancer
  • Metastatic Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • liver metastases
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary

Name

Location
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182