HAI Irinotecan + IV Bevacizumab, Bevacizumab & Oxaliplatin or Bevacizumab & Cetuximab in Advanced Cancers Metastatic to Liver
A Multi-arm Phase I Trial of Hepatic Arterial Infusion of Irinotecan With 1) Systemic Bevacizumab 2) Systemic Bevacizumab and Oxaliplatin 3) Systemic Bevacizumab and Cetuximab in Patients With Advanced Cancers Metastatic to the Liver
2 other identifiers
interventional
115
1 country
1
Brief Summary
The goal of this clinical research study is to learn the highest tolerable dose of irinotecan that can be given directly into the liver, in combination with other drugs given by vein. The other drug combinations given by vein include bevacizumab alone, bevacizumab plus oxaliplatin, and bevacizumab plus cetuximab. This will be tested in patients with advanced solid tumors that have spread to the liver. The safety of these 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 Sep 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
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 17, 2009
CompletedFirst Posted
Study publicly available on registry
September 21, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2015
CompletedNovember 11, 2015
November 1, 2015
5.9 years
September 17, 2009
November 9, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Doses (MTDs)
MTD is defined as the highest dose level at which ≥ 33% of patients have a DLT if \>3 patients are treated at that dose level or \> 33% have a DLT if ≤3 patients have been treated.
Evaulated with each 28 day cycle
Dose-limiting toxicities (DLTs)
DLT defined as any grade 3 or 4 non-hematologic toxicity defined in NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; 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; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.
Evaulated with each 28 day cycle
Study Arms (3)
Group 1
EXPERIMENTALGroup 1 = Irinotecan + Bevacizumab
Group 2
EXPERIMENTALGroup 2 = Irinotecan, Bevacizumab + Oxaliplatin
Group 3
EXPERIMENTALGroup 3 = Irinotecan, Bevacizumab + Cetuximab
Interventions
Starting dose of 35 mg/m\^2 given through the catheter into your liver artery (hepatic artery infusion - HAI), continuously for 72 hours (Days 1 through 2 of each cycle).
10 mg/Kg by vein on Days 1 and 15 of every 28 day cycle, over 90 minutes first cycle and over 30-60 minutes subsequent cycles.
Starting dose 60 mg/m\^2 by vein over 2 hours on Days 1 and 15 of every cycle.
500 mg/m\^2 by vein on Days 1 and 15 of every cycle. The first time given over 2 hours, all other cycles over 1 hour.
Eligibility Criteria
You may qualify if:
- Patients with histologically confirmed metastatic advanced cancers with liver involvement.
- Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months, unless the drugs included in the regimen are part of their standard treatment.
- Irinotecan will be dosed regardless of creatinine clearance. For oxaliplatin, serum creatinine \</= 2.5 times the upper limit of normal or creatinine clearance \>/= 40 is required.
- Hepatic function: T. Bilirubin \</= 3 mg/dl, ALT \</= 5X upper limit of normal (ULN).
- Adequate bone marrow function (ANC \>/=1000 cells/uL; PLT \>/= 100,000 cells/uL).
- Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (\<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available.
- All females in childbearing age MUST have a negative serum or urine pregnancy 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.
- Eastern Cooperative Oncology Group (ECOG) Performance status \</= 2.
You may not qualify if:
- Pregnant females.
- Patients with colorectal cancer and K-RAS mutation will be excluded from the cetuximab arm.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- Invasive procedures defined as follows: a. Major surgical procedure within 28 days prior to Day 1 therapy. b. Anticipation of need for major surgical procedures during the course of the study.
- Patients receiving any other investigational agents.
- Patients with bleeding diathesis (clinical bleeding, prothrombin time \>/= 1.5 X upper institutional normal value, international normalized ratio (INR) \>/=1.5, activated partial thromboplastin time aPTT \>/= 1.5 X upper institutional normal value, NOT due to anticoagulation therapy), active gastric or duodenal ulcer.
- Patients with history of bleeding CNS metastasis will be excluded from the trial.
- Hypersensitivity to any of the drugs in a particular treatment arm.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow up requirements.
- History of heparin-induced thrombocytopenia.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg on medication).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Apostolia M. Tsimberidou, MD, PhD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 17, 2009
First Posted
September 21, 2009
Study Start
September 1, 2009
Primary Completion
August 1, 2015
Study Completion
August 1, 2015
Last Updated
November 11, 2015
Record last verified: 2015-11