Combination Chemotherapy With or Without Chemoembolization in Treating Patients With Colorectal Cancer Metastatic to the Liver

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00023868
Recruitment Status : Completed
First Posted : June 17, 2003
Last Update Posted : January 6, 2009
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. It is not yet known if chemoembolization is more effective than standard chemotherapy in treating metastatic cancer.

PURPOSE: This phase I trial and randomized phase III trial is studying the effectiveness of chemoembolization in treating patients who have colorectal cancer metastatic to the liver.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Cancer Drug: FOLFIRI regimen Drug: cisplatin Drug: doxorubicin hydrochloride Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: mitomycin C Phase 3

Detailed Description:


  • Compare the survival of patients with liver-dominant metastatic colorectal adenocarcinoma treated with irinotecan, fluorouracil, and leucovorin calcium with or without hepatic chemoembolization.
  • Compare response in the liver, time to hepatic tumor progression, and time to extrahepatic tumor progression in patients treated with these regimens.
  • Compare the possible treatment differences with respect to morbidity, toxic effects of chemoembolization, toxic effects of chemotherapy, and death from cancer-related complications in these patients.

OUTLINE: This is a phase I dose-escalation study followed by a phase III randomized, multicenter study. (Phase I closed as of 10/14/02.)

  • Phase I: Patients in phase I are sequentially enrolled to 1 of 3 treatment regimens. (Phase I closed as of 10/14/02.)

    • Regimen A: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium IV, and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Patients undergo hepatic embolization with embolic suspension only on day 36.
    • Regimen B: Patients receive chemotherapy as in regimen A. Patients undergo hepatic chemoembolization with lower-dose cisplatin, doxorubicin, and mitomycin on day 36.
    • Regimen C: Patients receive chemotherapy as in regimen A. Patients undergo hepatic chemoembolization with higher-dose cisplatin, doxorubicin, and mitomycin on day 36.

After 1 week of rest, patients in all regimens receive a second 4-week course of systemic chemotherapy.

Cohorts of 3-10 patients are sequentially enrolled until the maximum tolerated dose (MTD) of chemotherapy and chemoembolization is determined. The MTD is defined as the dose preceding that at which at least 4 of 10 patients experience dose-limiting toxicity.

  • Phase III: Patients are stratified according to liver volume involvement (less than 25% vs 25-50% vs more than 50% to less than 75%) and participating center. Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium IV, and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Courses repeat every 6 weeks in the absence of disease progression.
    • Arm II: Patients receive chemotherapy as in arm I. Patients undergo hepatic chemoembolization with cisplatin, doxorubicin, and mitomycin on day 36. Chemotherapy repeats every 6 weeks in the absence of disease progression. Chemoembolization may repeat every 6 weeks for 2-4 courses as necessary.

Patients in phase III are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for phase I of this study. (Phase I closed to accrual as of 10/14/02.) Approximately 315 patients will be accrued for phase III of this study within 2.5 years.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Phase I/III Study Of Systematic Chemotherapy With Or Without Hepatic Chemoembolization For Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum
Study Start Date : November 2001

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed metastatic colorectal adenocarcinoma

    • Measurable metastasis to liver at least 1.0 cm

      • Less than 75% of total liver volume
    • Known extrahepatic disease limited to lymph nodes and less than 2 cm
    • No ascites
  • Ineligible for surgery



  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified


  • Absolute granulocyte count at least 2,000/mm^3
  • Platelet count at least 90,000/mm^3
  • No bleeding diathesis not correctable by standard therapy


  • Ineligible if all of the following criteria are concurrently present:

    • High risk of hepatic failure (more than 50% liver involvement by tumor)
    • Bilirubin greater than 2.0 mg/dL
    • SGOT greater than 100 U/L
    • Lactate dehydrogenase greater than 425 U/L
  • No hepatic encephalopathy
  • No portal vein occlusion without hepatopedal collateral flow demonstrated by angiography
  • No portal hypertension with hepatofugal flow


  • Creatinine no greater than 2.0 mg/dL


  • No myocardial infarction within the past 6 months
  • No evidence of congestive heart failure
  • No severe peripheral vascular disease that would preclude catheterization


  • No severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Fertile patients must use effective contraception


Biologic therapy:

  • No more than 1 prior adjuvant immunotherapy regimen for colon cancer


  • At least 6 months since prior adjuvant chemotherapy and recovered
  • No more than 1 prior adjuvant chemotherapy regimen for colon cancer
  • No prior hepatic arterial infusion chemotherapy

Endocrine therapy:

  • Not specified


  • At least 1 month since prior radiotherapy
  • No prior hepatic radiotherapy


  • At least 1 month since prior surgery
  • Prior surgical resection or ablation of liver metastases allowed


  • No other concurrent therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00023868

United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New York
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
American College of Radiology Imaging Network
National Cancer Institute (NCI)
Study Chair: Michael C. Soulen, MD Abramson Cancer Center of the University of Pennsylvania Identifier: NCT00023868     History of Changes
Other Study ID Numbers: CDR0000068871
First Posted: June 17, 2003    Key Record Dates
Last Update Posted: January 6, 2009
Last Verified: December 2003

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
liver metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors