Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Intravenous Oxaliplatin Plus Irinotecan in Patients With Unresectable Hepatic Metastases From Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center University of Medicine and Dentistry New Jersey Sanofi-Aventis
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00695201

Purpose

The purpose of this study is to see how well patients tolerate the side effects of treatment with Floxuridine, Oxaliplatin and Irinotecan. We also want to know if these methods used together are a useful way of treating cancer. We have studied these drugs and know the best doses of each when they are used alone. We do not yet know how well the drugs work with each other. This study will tell us the best doses of each drug when they are given over the same period of time.

Condition	Intervention	Phase
Colon Cancer Rectal Cancer	Drug: Floxuridine, Oxaliplatin, CPT-11	Phase I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Irinotecan Irinotecan hydrochloride Floxuridine Oxaliplatin Heparin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Intravenous Oxaliplatin Plus Irinotecan in Patients With Unresectable Hepatic Metastases From Colorectal Cancer.

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

Determine the MTD of hepatic arterial floxuridine (FUDR) & dexamethasone (Dex) given via implanted pump in combination w biweekly intravenous Oxaliplatin + systemic irinotecan (CPT-11) in patients w unresectable hepatic metastases from colorectal cancer. [ Time Frame: conclusion of the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the preliminary anti-tumor activity of the aforementioned combination chemotherapy. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
To procure normal and disease liver tissue for evaluation of TS, p53, p21, TOPO 1, DPD, and ERCC levels. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	August 2000
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Patients will undergo pump placement and biopsy of diseased liver tissue. Chemotherapy will be initiated as soon as possible following verification of adequate pump placement and perfusion by radiographic pump study. Treatment will continue indefinitely unless a patient experiences a treatment endpoint.	Drug: Floxuridine, Oxaliplatin, CPT-11 For patients on the 4-week cycle: On the first day of each cycle, the pump will be filled with FUDR and dexamethasone. The pump will be emptied of drugs after 2 weeks (on day 15 of each cycle) and filled with heparin (which is used to prevent blood from clotting) and saline. Whether the pump contains drug or heparin and saline, it will need to be emptied and refilled about every two weeks. We will inject either the drugs or the saline and heparin into the pump through the skin using a needle and syringe. In summary, 2 weeks of drug in the pump is followed by 2 weeks without drug in the pump. The systemic chemotherapy (Oxaliplatin/CPT-11) will be administered on the same day as the pump is filled and emptied, ie. Day 1 and Day 15 of each cycle.
2: Experimental Patients will undergo pump placement and biopsy of diseased liver tissue. Chemotherapy will be initiated as soon as possible following verification of adequate pump placement and perfusion by radiographic pump study. Treatment will continue indefinitely unless a patient experiences a treatment endpoint.	Drug: Floxuridine, Oxaliplatin, CPT-11 For patients on the 5-week cycle: On the first day of each cycle, the pump will be filled with FUDR and dexamethasone. The pump will be emptied of drugs after 2 weeks (on day 15 of each cycle) and filled with heparin and saline. This is repeated on day 29 of each cycle). In summary, 2 weeks of drug in the pump are followed by 3 weeks without drug in the pump. The systemic chemotherapy (Oxaliplatin/CPT-11) will be administered on the same day that the pump is emptied and filled with heparin and saline, i.e. Day 15 and Day 29 of each cycle.

Arms

Assigned Interventions

1: Experimental

Patients will undergo pump placement and biopsy of diseased liver tissue. Chemotherapy will be initiated as soon as possible following verification of adequate pump placement and perfusion by radiographic pump study. Treatment will continue indefinitely unless a patient experiences a treatment endpoint.

Drug: Floxuridine, Oxaliplatin, CPT-11

For patients on the 4-week cycle: On the first day of each cycle, the pump will be filled with FUDR and dexamethasone. The pump will be emptied of drugs after 2 weeks (on day 15 of each cycle) and filled with heparin (which is used to prevent blood from clotting) and saline. Whether the pump contains drug or heparin and saline, it will need to be emptied and refilled about every two weeks. We will inject either the drugs or the saline and heparin into the pump through the skin using a needle and syringe. In summary, 2 weeks of drug in the pump is followed by 2 weeks without drug in the pump. The systemic chemotherapy (Oxaliplatin/CPT-11) will be administered on the same day as the pump is filled and emptied, ie. Day 1 and Day 15 of each cycle.

2: Experimental

Patients will undergo pump placement and biopsy of diseased liver tissue. Chemotherapy will be initiated as soon as possible following verification of adequate pump placement and perfusion by radiographic pump study. Treatment will continue indefinitely unless a patient experiences a treatment endpoint.

Drug: Floxuridine, Oxaliplatin, CPT-11

For patients on the 5-week cycle: On the first day of each cycle, the pump will be filled with FUDR and dexamethasone. The pump will be emptied of drugs after 2 weeks (on day 15 of each cycle) and filled with heparin and saline. This is repeated on day 29 of each cycle). In summary, 2 weeks of drug in the pump are followed by 3 weeks without drug in the pump. The systemic chemotherapy (Oxaliplatin/CPT-11) will be administered on the same day that the pump is emptied and filled with heparin and saline, i.e. Day 15 and Day 29 of each cycle.

Eligibility

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

Criteria

Inclusion Criteria:

History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease.

Confirmation of diagnosis must be performed at MSKCC.

Patient's liver metastases must be deemed unresectable and comprise <70% of the liver parenchyma.
A patient may have had prior chemotherapy or be previously untreated.
Patient may not have received prior treatment with FUDR or >2 doses of Oxaliplatin.
KPS > or = to 60%.
WBC > or = to 3,000 cells/mm3 and platelet count > or = to 100,000 cells/mm3 within 14 days of registration.
Creatinine < or = to 1.5 mg/dl within 14 days of registration.
Total serum bilirubin < or = 2.0 mg/dl within 14 days of registration.

Exclusion Criteria:

No active concurrent malignancies: except a patient's potentially resectable colorectal primary.
Patient must not have obstruction of GI or GU tract.
Patient must not have current, symptomatic peripheral sensory neuropathy.
No prior radiation to liver.
No active infection, ascites, or hepatic encephalopathy.
Age ≥ 18 years.
Female patients cannot be pregnant or lactating.
Signed informed consent.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00695201

Locations

United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

University of Medicine and Dentistry New Jersey

Sanofi-Aventis

Investigators

Principal Investigator:

Nancy Kemeny, MD

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Nancy Kemeny, MD )
Study ID Numbers:	00-011
Study First Received:	June 9, 2008
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00695201
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

DEXAMETHASONE
FLOXURIDINE
IRINOTECAN (CPT-11) CAMPTOSAR
OXALIPLATIN

Study placed in the following topic categories:

Dexamethasone
Digestive System Neoplasms
Floxuridine
Rectal Neoplasms
Gastrointestinal Diseases
Irinotecan
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Calcium heparin

Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Neoplasm Metastasis
Gastrointestinal Neoplasms
Heparin
Colonic Neoplasms
Rectal cancer
Dexamethasone acetate
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Enzyme Inhibitors
Hormones

Glucocorticoids
Pharmacologic Actions
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009