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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00507585
First received: July 24, 2007
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

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.

Condition Intervention Phase
Liver Cancer
Advanced Solid Tumors
Drug: Fluorouracil
Drug: Avastin
Drug: Leucovorin
Drug: Oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients With Advanced Solid Tumors Metastatic to the Liver

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]

Enrollment: 63
Study Start Date: June 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxaliplatin + Fluorouracil + Leucovorin + Avastin Drug: Fluorouracil
300 mg/m^2 IV over 10 Minutes, then 600 mg/m^2 IV over 22 Hours repeated every 3 weeks (1 Cycle).
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
  • 5-fluorouracil
Drug: Avastin
10 mg/m^2 IV Over 90 Minutes repeated every 3 weeks (1 Cycle).
Other Name: Bevacizumab
Drug: Leucovorin
200 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).
Drug: Oxaliplatin
60 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically confirmed metastatic advanced solid tumors involving the liver.
  2. Pediatric patients eligible at the discretion of the primary investigator.
  3. Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any work activities).
  4. Adequate renal function (Serum Creatinine </= 2.0 mg/dL) or a calculated creatinine clearance greater than 60 mL/min.
  5. 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.
  6. Adequate bone marrow function (ANC >/=1500 cells/uL; PLT >/= 100,000 cells/uL).
  7. 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.
  8. 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.
  9. Ability to fully read, comprehend, and sign informed consent forms.

Exclusion Criteria:

  1. Clinical or radiographic evidence of ascites.
  2. Pregnant females.
  3. Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
  4. Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function but not interfering with ADL)
  5. Serious or non-healing wound, ulcer or bone fracture.
  6. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
  7. 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.
  8. Patients receiving any other investigational agents.
  9. 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.
  10. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
  11. 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.
  12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  13. 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
  14. Patients with history of bleeding CNS metastasis will be excluded from the trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507585

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Apostolia M. Tsimberidou, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00507585     History of Changes
Other Study ID Numbers: 2006-0160
Study First Received: July 24, 2007
Last Updated: July 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Liver Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Fluorouracil
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014