Safety Study of Oxaliplatin and 5-fluorouracil Followed by FUDR for Unresectable Colorectal Liver Metastases

NCT00557557 | Completed Phase 1 DMC

• 2 other identifiers: 05-0961R21CA115059-01A1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Liver Metastases

Keywords

Colorectal; liver; cancer; metastases

Outcome Measures

Primary Outcomes (1)

• Primary endpoint is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU delivered with 40mg/m² of Oxaliplatin via IHP.

  24 to 48 hours

Secondary Outcomes (1)

• Secondary endpoints will be to determine the response rate and survival after IHP with 5-FU and Oxaliplatin.

  3 to 6 months

Study Arms (1)

IHP with Oxaliplatin and 5-Fluorouracil (5-FU)

EXPERIMENTAL

Isolated Hepatic Perfusion with Oxaliplatin and 5-Fluorouracil (5-FU)

Drug: Drug: 5-FU; Drug: Drug: Oxaliplatin

Interventions

Drug: 5-FU DRUG

Dose escalation (200 to 900 mg/m²) scheme, one hour isolated hepatic perfusion prior to standard treatment.

IHP with Oxaliplatin and 5-Fluorouracil (5-FU)

Drug: Oxaliplatin DRUG

40 mg/m², one hour isolated hepatic perfusion prior to standard treatment.

IHP with Oxaliplatin and 5-Fluorouracil (5-FU)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven measurable metastatic colorectal cancer limited to the parenchyma of the liver by preoperative radiological studies. Limited resectable extrahepatic disease is acceptable if the liver is felt to be the dominate site of life threatening disease.
• No chemotherapy, radiotherapy, or biologic therapy for their malignancy in the 4 weeks prior to the liver perfusion and must have recovered from all side effects.
• An ECOG performance standard of 0, 1 or 2 for 24 hours prior to surgery.
• Adequate hepatic function as evidenced by bilirubin \< 2.0 mg/dL and a PT \< 2 seconds greater than the upper limit of normal.
• Age equal to 18 years or older and greater than 30 kg.
• Platelet counts greater than 100,000, a hematocrit \> 27.0, a white blood count \> 3000/µl, Absolute neutrophil count \> 1,500/μL and a creatinine less than or equal to 1.5 mg/dL or a creatinine clearance of \> 60 mL/min. Patients with elevations in hepatic transaminases secondary to the presence of metastatic disease in the liver are eligible.
• Adequate hepatic function as evidenced by:
• Serum total bilirubin \< 1.5 mg/dL
• Alkaline phosphatase \< 5X the ULN
• SGOT/SGPT \< 5X the ULN
• Aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks and willing to sign an informed consent.
• The disease in the liver must be considered unresectable as defined by greater than three sites of disease in the liver, bilobar disease, and tumor abutting major vascular or ductal structures making anatomic resection with preservation of liver function impossible.
• Patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication

You may not qualify if:

• 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.

Sponsors & Collaborators

• David Bartlett: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UPMC Cancer Centers Network

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Herbert J. Zeh, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Surgical Oncology

Study Record Dates

• First Submitted: November 13, 2007
• First Posted: November 14, 2007
• Study Start: July 1, 2007
• Primary Completion: March 1, 2012
• Study Completion: August 1, 2014
• Last Updated: December 28, 2015

Record last verified: 2015-12

Locations

US (1)