Combination Chemotherapy in Treating Patients With Unresectable Liver Metastases From Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00008294

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer Metastatic Cancer	Drug: FOLFOX regimen Drug: dexamethasone Drug: floxuridine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase I

Study Type:	Interventional
Study Design:	Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Dexamethasone Floxuridine Fluorouracil Leucovorin Citrovorum factor Dexamethasone acetate Oxaliplatin Doxiproct plus Leucovorin Calcium Dexamethasone Sodium Phosphate Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

August 2000

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008294

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Nancy E. Kemeny, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Kemeny N, Jarnagin W, Paty P, Gonen M, Schwartz L, Morse M, Leonard G, D'Angelica M, DeMatteo R, Blumgart L, Fong Y. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005 Aug 1;23(22):4888-96. Epub 2005 Jul 11.

Study ID Numbers:	CDR0000068395, MSKCC-00009, NCI-G00-1896
Study First Received:	January 6, 2001
Last Updated:	January 10, 2009
ClinicalTrials.gov Identifier:	NCT00008294 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

liver metastases
recurrent colon cancer
recurrent rectal cancer

Study placed in the following topic categories:

Antimetabolites
Anti-Inflammatory Agents
Dexamethasone
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Hormone Antagonists
Colonic Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Leucovorin
Antiemetics
Hormones
Rectal Diseases
Oxaliplatin
Vitamins

Neoplasm Metastasis
Micronutrients
Dexamethasone acetate
Vitamin B Complex
Digestive System Neoplasms
Antineoplastic Agents, Hormonal
Floxuridine
Rectal Neoplasm
Trace Elements
Folinic Acid
Intestinal Diseases
Immunosuppressive Agents
Glucocorticoids
Intestinal Neoplasms
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Dexamethasone
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Colonic Diseases
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Leucovorin
Antiemetics
Hormones
Rectal Diseases

Neoplastic Processes
Oxaliplatin
Neoplasms by Site
Pathologic Processes
Vitamins
Therapeutic Uses
Neoplasm Metastasis
Micronutrients
Dexamethasone acetate
Vitamin B Complex
Digestive System Neoplasms
Antineoplastic Agents, Hormonal
Floxuridine
Growth Substances
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 02, 2009