Hepatic Arterial Infusion Oxaliplatin + 5FU, Leucovorin, and Bevacizumab +/- Cetuximab
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
2 other identifiers
interventional
140
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2009
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2009
CompletedFirst Submitted
Initial submission to the registry
July 15, 2009
CompletedFirst Posted
Study publicly available on registry
July 17, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2014
CompletedNovember 18, 2015
November 1, 2015
4.8 years
July 15, 2009
November 16, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin
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.
21 days
Anti-Tumor Efficacy
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.
After 2, 21 day cycles
Study Arms (4)
Group 1
EXPERIMENTALHAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab
Group 2
EXPERIMENTALHAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
Group 3
EXPERIMENTALHAI oxaliplatin in combination with IV bevacizumab.
Group 4
EXPERIMENTALHAI oxaliplatin in combination with IV bevacizumab and cetuximab.
Interventions
140 mg/m\^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
900-1750 mg/m\^2 HAI infusion over 24 hours on Days 1 - 2 of each 21 day cycle.
10 mg/Kg by vein on Day 1 of 21 day cycle.
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.
200 mg/m\^2 by vein on Days 1 and 2 of each 21 day cycle.
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed cancer with metastatic liver metastases.
- 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.
- 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).
- Adequate renal function (Serum Creatinine \</= 2.0 mg/dL). Pediatric: serum creatinine \</= 1.5 mg/dL or 2x upper limit of normal, for age.
- 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.
- Adequate bone marrow function (Absolute Neutrophil Count (ANC) \>/=1500 cells/uL; Platelets (PLT) \>/= 100,000 cells/uL).
- 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.
- 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.
- Ability to sign informed consent form. Pediatric: age 7-18 would sign assent, (\<7 would not assent), parent or guardian would sign consent.
- 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.
You may not qualify if:
- Pregnant females.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, Diastolic Blood Pressure \> 90 mmHg).
- 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.
- Patients already in uncompensated liver failure (i.e. Child Pugh Liver Classification C).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Apostolia M. Tsimberidou, MD, PHD
UT MD Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 15, 2009
First Posted
July 17, 2009
Study Start
July 1, 2009
Primary Completion
May 1, 2014
Study Completion
May 1, 2014
Last Updated
November 18, 2015
Record last verified: 2015-11