Hepatic Arterial Infusion Oxaliplatin + 5FU, Leucovorin, and Bevacizumab +/- Cetuximab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00941499
First received: July 15, 2009
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to find the best combination of oxaliplatin, bevacizumab, 5-fluorouracil, leucovorin, and cetuximab that can be given to patients with advanced cancer that has spread to the liver. Different combinations of these drugs will be used, and the safety of all drug combinations will also be studied.


Condition Intervention Phase
Advanced Cancers
Drug: HAI Oxaliplatin
Drug: 5-FU
Drug: Bevacizumab
Drug: Cetuximab
Drug: Leucovorin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Bevacizumab With/Without Cetuximab by K-RAS Mutational Status and Liver Function for Advanced Cancers Metastatic to the Liver

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    If more than 33% of patients enrolled in any particular dose level develop DLT, the treatment will continue at the dose level immediately below. If not more than 33% of the patients in the cohort develop DLT, this cohort will be considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v3.0, any Grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI CTC), despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in the NCI CTC. The MTD defined by DLTs that occur in the first cycle.

  • Anti-Tumor Efficacy [ Time Frame: After 2, 21 day cycles ] [ Designated as safety issue: No ]
    Response Evaluation Criteria in Solid Tumors (RECIST) guidelines used to assess the efficacy of this regimen. A 20% increase in the sum of the greatest longitudinal diameters considered stable disease in the absence of clinical symptoms. An exploratory analysis of radiographic tool measuring the diameter of tumor lesions and comparing their tissue density in comparison with liver function studies and serum biochemical markers performed among study participants.


Enrollment: 140
Study Start Date: July 2009
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
HAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab
Drug: HAI Oxaliplatin
140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
Other Name: Eloxatin
Drug: 5-FU
900-1750 mg/m^2 HAI infusion over 24 hours on Days 1 - 2 of each 21 day cycle.
Other Names:
  • 5-Fluorouracil
  • Adrucil
  • Efudex
Drug: Bevacizumab
10 mg/Kg by vein on Day 1 of 21 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Experimental: Group 2
HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
Drug: HAI Oxaliplatin
140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
Other Name: Eloxatin
Drug: Bevacizumab
10 mg/Kg by vein on Day 1 of 21 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Leucovorin
200 mg/m^2 by vein on Days 1 and 2 of each 21 day cycle.
Other Names:
  • Citrovorum
  • Wellcovorin
Drug: 5-FU
300-400 mg/m^2 bolus + 600-1000 mg/m^2 infusion over 22 hours on Days 1-2 of each cycle.
Other Names:
  • 5-Fluorouracil
  • Adrucil
  • Efudex
Experimental: Group 3
HAI oxaliplatin in combination with IV bevacizumab.
Drug: HAI Oxaliplatin
140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
Other Name: Eloxatin
Drug: Bevacizumab
10 mg/Kg by vein on Day 1 of 21 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Experimental: Group 4
HAI oxaliplatin in combination with IV bevacizumab and cetuximab.
Drug: HAI Oxaliplatin
140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
Other Name: Eloxatin
Drug: Cetuximab
Loading dose of 250-500mg/m^2 and Maintenance dose of 125-250 mg/m^2 by vein on Day 1 of 21 day cycle.
Other Names:
  • C225
  • Erbitux
  • IMC-C225
Drug: Bevacizumab
7.5 - 15 mg/Kg by vein on Day 1 of 21 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Patients must have histologically confirmed cancer with metastatic liver metastases.
  2. Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months, unless the drugs in the protocol regimen are part of the standard of care.
  3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (Capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
  4. Adequate renal function (Serum Creatinine </= 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
  5. Patients will be stratified by liver function tests: Normal liver function: Total Bilirubin </= 3 mg/dL, Alanine aminotransferase (ALT) </= 5 times upper normal reference value. Abnormal liver function: Total bilirubin >3 mg/dL and/or elevated ALT > 5 x upper limit of normal (ULN). If bilirubin is >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted. Both of the above groups will be eligible.
  6. Adequate bone marrow function (Absolute Neutrophil Count (ANC) >/=1500 cells/uL; Platelets (PLT) >/= 100,000 cells/uL).
  7. At least three weeks from previous cytotoxic chemotherapy before day 1 of hepatic arterial infusion (HAI) infusion. After targeted or biologic therapy, there should be 5 half-lives or three weeks, whichever is shorter.
  8. All females in childbearing age MUST have a negative urine human chorionic gonadotropin (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 sign informed consent form. Pediatric: age 7-18 would sign assent, (<7 would not assent), parent or guardian would sign consent.
  10. Patients with colorectal cancer must agree to K-RAS mutational status screening, if not available. If tissue is not available, patients can enter on trial, but not on the cetuximab arms.

Exclusion Criteria:

  1. Pregnant females.
  2. Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
  3. Serious or non-healing wound, ulcer or bone fracture.
  4. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
  5. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Patients already in uncompensated liver failure (i.e. Child Pugh Liver Classification C).
  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: NCT00941499

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Apostolia M. Tsimberidou, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00941499     History of Changes
Other Study ID Numbers: 2009-0023, NCI-2011-00538
Study First Received: July 15, 2009
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Liver
Oxaliplatin
Eloxatin
Bevacizumab
Avastin
Anit-VEGF monoclonal antibody
rhuMAb-VEGF
5-fluorouracil
5-FU
Adrucil
Efudex
Leucovorin
Citrovorum
Wellcovorin
Cetuximab
C225
Erbitux
IMC-C225

Additional relevant MeSH terms:
Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Cetuximab
Fluorouracil
Immunoglobulins
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014