Clinical trial NCT00023868: Combination Chemotherapy With or Without Chemoembolization in Treating Patients With Colorectal Cancer Metastatic to the Liver (6655)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colorectal Cancer
Metastatic Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
liver metastases
Lead sponsor: American College of Radiology Imaging Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVES:

* 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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-2

Life expectancy:

* Not specified

Hematopoietic:

* 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

Hepatic:

* 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

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

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

Other:

* 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

Chemotherapy:

* 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

Radiotherapy:

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

Surgery:

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

Other:

* No other concurrent therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Michael C. Soulen, MD
role: STUDY_CHAIR
References: