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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00695201

Collaborator

University of Medicine and Dentistry of New Jersey (Other), Rutgers, The State University of New Jersey (Other), Sanofi (Industry)

Enrollment

Location

Arms

250.9

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Colon Cancer Rectal Cancer	Drug: Floxuridine, Oxaliplatin, CPT-11 Drug: Floxuridine, Oxaliplatin, CPT-11	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

Aug 1, 2000

Actual Primary Completion Date :

Jun 28, 2021

Actual Study Completion Date :

Jun 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 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.
Experimental: 2 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.

Arm

Intervention/Treatment

Experimental: 1

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.

Experimental: 2

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.

Outcome Measures

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. [conclusion of the study]

Secondary Outcome Measures

To determine the preliminary anti-tumor activity of the aforementioned combination chemotherapy. [conclusion of the study]
To procure normal and disease liver tissue for evaluation of TS, p53, p21, TOPO 1, DPD, and ERCC levels. [conclusion of the study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.