Safety Study of Oxaliplatin and 5-fluorouracil Followed by FUDR for Unresectable Colorectal Liver Metastases
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
David Bartlett, University of Pittsburgh
First received: November 13, 2007
Last updated: December 2, 2013
Last verified: December 2013
The purpose of this study is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU in combination with Oxaliplatin delivered via isolated hepatic perfusion.
Colorectal Liver Metastases
Drug: Drug: 5-FU
Drug: Drug: Oxaliplatin
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I Trial of Isolated Hepatic Perfusion With Oxaliplatin and 5-fluorouracil (5-FU) Followed by Hepatic Arterial Infusion of FUDR for Patients With Unresectable Colorectal Liver Metastases
Primary Outcome Measures:
- Primary endpoint is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU delivered with 40mg/m² of Oxaliplatin via IHP. [ Time Frame: 24 to 48 hours ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Secondary endpoints will be to determine the response rate and survival after IHP with 5-FU and Oxaliplatin. [ Time Frame: 3 to 6 months ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Primary Completion Date:
||March 2012 (Final data collection date for primary outcome measure)
Experimental: IHP with Oxaliplatin and 5-Fluorouracil (5-FU)
Isolated Hepatic Perfusion with Oxaliplatin and 5-Fluorouracil (5-FU)
Drug: Drug: 5-FU
Dose escalation (200 to 900 mg/m²) scheme, one hour isolated hepatic perfusion prior to standard treatment.
Drug: Drug: Oxaliplatin
40 mg/m², one hour isolated hepatic perfusion prior to standard treatment.
Subjects who are planning to undergo surgery for placement of HAI therapy pump will be considered for enrollment. Standard HAI therapy requires a laparotomy and placement of an intrahepatic arterial catheter that is connected to one of several commercially available subcutaneous electronic pumps. The pump is then used to deliver FUDR directly to the liver, usually beginning four weeks after surgery and lasts on average for a period of six to twelve months after the study. Current HAI therapy regimens often alternate FUDR with systemic chemotherapy. This study will examine the addition of a one hour isolated hepatic perfusion with 5-FU and Oxaliplatin prior to this standard treatment. Subjects will be given the consent form to review and after sufficient time to review the information, interested subjects will have the opportunity to ask questions of the investigators. Subjects interested in enrolling in the trial will then sign informed consent and clinical data will be collected from their chart to ensure that they meet eligibility requirements. The study will consist of a one hour isolated liver perfusion that will be performed at the time of the laparotomy to place the HAI therapy pump. Following surgery subjects will be monitored in the ICU for 24-48 hours and potentially in the hospital for an additional 5-7 days. Subjects will be free to start standard HAI therapy regimens four to six weeks following surgery. The duration of treatment, dose of HAI therapy and the decision to combine HAI with systemic chemotherapy will be at the discretion of the treating physician.
|Ages Eligible for Study:
||18 Years to 80 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Pregnant patients and nursing mothers will be excluded due to the unknown effects of oxaliplatin on the fetus or newborn.
- Patients with active CNS metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for >3 weeks are eligible for the trial.
- Patients taking immunosuppressive drugs or on chronic anticoagulation will not be eligible.
- Patients with active infections or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment are not eligible.
- Patients with biopsy proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices on endoscopy, or radiologic studies showing significant collateral vessels around the organs drained by the portal venous system will be excluded.
- Patients with ischemic cardiac disease or history of congestive heart failure with an LVEF < 40% will be excluded.
- Patients with COPD or other chronic pulmonary disease with PFTs indicating an FEV< 50% predicted for age will be excluded.
- Patients with a history of veno-occlusive disease of the liver are ineligible.
- History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry.
- Patients with known hypersensitivity to any of the components of oxaliplatin (or combination drug, if any).
- Patients who received radiotherapy to more than 25% of their bone marrow; or patients who received any radiotherapy within 4 weeks of entry.
- Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication).
- Peripheral neuropathy ≥ Grade 2.
- Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
- History of allogeneic transplant.
- Known HIV or Hepatitis B or C (active, previously treated or both).
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00557557
|UPMC Cancer Centers Network
|Pittsburgh, Pennsylvania, United States, 15232 |
||Herbert J. Zeh, MD
||University of Pittsburgh
No publications provided
||David Bartlett, Chief, Division of Surgical Oncology, University of Pittsburgh
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 13, 2007
||December 2, 2013
||United States: Food and Drug Administration
Keywords provided by University of Pittsburgh:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 20, 2014
Neoplasms, Second Primary
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs