Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, Leucovorin, and Avastin

NCT00507585 | Completed Phase 1

• 1 other identifier: 2006-0160
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

PRIMARY:

• To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver. SECONDARY:
• To document in a descriptive fashion the antitumor efficacy of this combination regimen.
• To evaluate the feasibility and accuracy of an alternate radiographic assessment tool and compare with available tumor markers and RECIST guidelines.
• To estimate in a descriptive fashion the development of extrahepatic tumor recurrences.

Conditions

Liver Cancer; Advanced Solid Tumors

Keywords

Liver Cancer; Liver metastases; Metastatic advanced solid tumors; Advanced solid tumors metastatic to the liver; Hepatic Arterial Infusion; Intra-arterial hepatic oxaliplatin; Fluorouracil; 5-FU; Adrucil; Efudex; 5-fluorouracil; Avastin; Leucovorin; Oxaliplatin; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver.

  5 Years

Study Arms (1)

Oxaliplatin + Fluorouracil + Leucovorin + Avastin

EXPERIMENTAL

Drug: Fluorouracil; Drug: Avastin; Drug: Leucovorin; Drug: Oxaliplatin

Interventions

Fluorouracil DRUG

300 mg/m\^2 IV over 10 Minutes, then 600 mg/m\^2 IV over 22 Hours repeated every 3 weeks (1 Cycle).

Also known as: 5-FU, Adrucil, Efudex, 5-fluorouracil

Oxaliplatin + Fluorouracil + Leucovorin + Avastin

Avastin DRUG

10 mg/m\^2 IV Over 90 Minutes repeated every 3 weeks (1 Cycle).

Also known as: Bevacizumab

Oxaliplatin + Fluorouracil + Leucovorin + Avastin

Leucovorin DRUG

200 mg/m\^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).

Oxaliplatin + Fluorouracil + Leucovorin + Avastin

Oxaliplatin DRUG

60 mg/m\^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).

Oxaliplatin + Fluorouracil + Leucovorin + Avastin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed metastatic advanced solid tumors involving the liver.
• Pediatric patients eligible at the discretion of the primary investigator.
• Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any work activities).
• Adequate renal function (Serum Creatinine \</= 2.0 mg/dL) or a calculated creatinine clearance greater than 60 mL/min.
• Hepatic function as follows: In treatment arm 1: Total Bilirubin \</= 3 mg/dL, AST \</= 5 times upper normal reference value, or ALT \</= 5 times upper normal reference value). In treatment arm 2: Total bilirubin \>3 mg/dL. If bilirubin \>/= 5 mg/dL, fluorouracil (5FU) dose will be omitted.
• Adequate bone marrow function (ANC \>/=1500 cells/uL; PLT \>/= 100,000 cells/uL).
• At least three weeks from previous immunotherapy, chemotherapy or radiotherapy before day of HAI infusion and recovery from any associated toxicities to less or equal to Grade 1.
• All females in childbearing age MUST have a negative serum HCG test unless prior hysterectomy or menopause (defined as age above 55 and six months without menstrual activity). Patients should not become pregnant or breast feed while on this study. Sexually active patients should use effective birth control.
• Ability to fully read, comprehend, and sign informed consent forms.

You may not qualify if:

• Clinical or radiographic evidence of ascites.
• Pregnant females.
• Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
• Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function but not interfering with ADL)
• Serious or non-healing wound, ulcer or bone fracture.
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
• Invasive procedures defined as follows; Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy, Anticipation of need for major surgical procedures during the course of the study, Core biopsy within 7 days prior to D1 of therapy.
• Patients receiving any other investigational agents.
• Patients with bleeding diathesis (clinical bleeding, prothrombin time =/\> 1.5 X upper institutional normal value, INR =/\> 1.5, activated partial thromboplastin time aPTT =/\> 1.5 X upper institutional normal value), active gastric or duodenal ulcer.
• Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, Diastolic Blood Pressure \> 90 mmHg).
• Urine protein should be screened by dipstick or urine analysis. For proteinuria \> 1+ or urine protein:creatinine ratio \> 1.0, a 24-hour urine protein should be obtained and the level should be \< 1000 mg for patient enrollment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with clinically significant cardiovascular disease: History of CVA within 6 months, myocardial infarction or unstable angina within 6 months, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris, clinically significant peripheral vascular disease
• Patients with history of bleeding CNS metastasis will be excluded from the trial.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Fluorouracil; Bevacizumab; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Apostolia M. Tsimberidou, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2007
• First Posted: July 26, 2007
• Study Start: June 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: July 30, 2012

Record last verified: 2012-07

Locations

US (1)