Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	Over 18	NCI	MSKCC-00009 NCI-G00-1896, NCT00008294

Objectives

1. 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.
2. Determine, preliminarily, the anti-tumor activity of this regimen in these patients.

Entry Criteria

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

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

Patient Characteristics:

Age:

• Over 18

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

Approximately 4-72 patients will be accrued for this study within 18 months.

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.

Kemeny N, Capanu M, D'Angelica M, et al.: Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer. Ann Oncol 20 (7): 1236-41, 2009.[PUBMED Abstract]

Kemeny N, Jarnagin W, Paty P, et al.: Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 23 (22): 4888-96, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Nancy Kemeny, MD, Protocol chair		Ph: 212-639-8068; 800-525-2225

Registry Information
Official Title		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
Trial Start Date		2000-08-16
Registered in ClinicalTrials.gov		NCT00008294
Date Submitted to PDQ		2000-11-21
Information Last Verified		2005-05-05
NCI Grant/Contract Number		P30-CA08748

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