Combination Chemotherapy in Treating Patients With Unresectable Liver Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Cryosurgery kills cancer cells by freezing them. Combining more than one chemotherapy drug with cryosurgery and giving drugs in different ways may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of intrahepatic and intravenous combination chemotherapy with or without cryosurgery in treating unresectable liver metastases from colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of oxaliplatin and fluorouracil when given with leucovorin calcium and hepatic intra-arterial floxuridine and dexamethasone with or without cryosurgery (group I cryosurgery closed to accrual as of 10/13/03) in patients with unresectable liver metastases from colorectal cancer. Determine, preliminarily, the anti-tumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil. Patients are assigned to one of two treatment groups. (Group I closed to accrual as of 10/13/03.) Group I (closed to accrual as of 10/13/03): Patients with no more than 8 hepatic metastases and no metastases greater than 5 cm in diameter undergo cryosurgery prior to chemotherapy. Chemotherapy is delayed for at least 4 weeks after cryosurgery. Group II: Patients with more than 8 hepatic metastases or at least one metastases greater than 5 cm in diameter do not undergo cryosurgery prior to chemotherapy. Beginning 2 weeks after pump placement surgery, all patients receive floxuridine and dexamethasone by hepatic intra-arterial infusion continuously on days 1-14; oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on days 15 and 29; and fluorouracil IV continuously over 48 hours on days 15-16 and 29-30. Courses repeat every 36 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: Approximately 4-72 patients will be accrued for this study within 18 months.

Official Title
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A Phase I Study Of Hepatic Arterial Infusion With Floxuridine And Dexamethasone In Combination With Intravenous Oxaliplatin Plus 5-Fluorouracil And Leucovorin In Patients With Unresectable Hepatic Metastases From Colorectal Cancer

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: dexamethasone
* Drug: floxuridine
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum with unresectable liver metastases that comprise less than 70% of liver parenchyma No extrahepatic disease No ascites PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2.0 mg/dL No hepatic encephalopathy Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test No obstruction of gastrointestinal tract or genitourinary tract No symptomatic peripheral sensory neuropathy No active infection No other malignancy except resectable primary colorectal carcinoma PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior floxuridine If undergoing cryosurgery (group I cryosurgery closed to accrual as of 10/13/03), must have received one of the following: Systemic chemotherapy for metastatic disease Adjuvant therapy within the past 6 months comprising fluorouracil with or without levamisole for resected primary colorectal carcinoma Adjuvant therapy within the past 12 months comprising fluorouracil and leucovorin calcium with or without levamisole for resected primary colorectal carcinoma Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to liver Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFOX regimen|nan|
|Drug: dexamethasone|nan|
|Drug: floxuridine|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, liver metastases, recurrent colon cancer, recurrent rectal cancer