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HAI Irinotecan + IV Bevacizumab, Bevacizumab & Oxaliplatin or Bevacizumab & Cetuximab in Advanced Cancers Metastatic to Liver

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00980239
First received: September 17, 2009
Last updated: November 9, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Advanced Cancer
Drug: Irinotecan
Drug: Bevacizumab
Drug: Oxaliplatin
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Doses (MTDs) [ Time Frame: Evaulated with each 28 day cycle ] [ Designated as safety issue: Yes ]
    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.

  • Dose-limiting toxicities (DLTs) [ Time Frame: Evaulated with each 28 day cycle ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 115
Study Start Date: September 2009
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Group 1 = Irinotecan + Bevacizumab
Drug: Irinotecan
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).
Other Names:
  • CPT-11
  • Camptosar
Drug: Bevacizumab
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.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Experimental: Group 2
Group 2 = Irinotecan, Bevacizumab + Oxaliplatin
Drug: Irinotecan
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).
Other Names:
  • CPT-11
  • Camptosar
Drug: Bevacizumab
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.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Oxaliplatin
Starting dose 60 mg/m^2 by vein over 2 hours on Days 1 and 15 of every cycle.
Other Name: Eloxatin
Experimental: Group 3
Group 3 = Irinotecan, Bevacizumab + Cetuximab
Drug: Irinotecan
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).
Other Names:
  • CPT-11
  • Camptosar
Drug: Bevacizumab
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.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Cetuximab
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.
Other Names:
  • C225
  • Erbitux
  • IMC-C225

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically confirmed metastatic advanced cancers with liver involvement.
  2. 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.
  3. 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.
  4. Hepatic function: T. Bilirubin </= 3 mg/dl, ALT </= 5X upper limit of normal (ULN).
  5. Adequate bone marrow function (ANC >/=1000 cells/uL; PLT >/= 100,000 cells/uL).
  6. 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.
  7. 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.
  8. Eastern Cooperative Oncology Group (ECOG) Performance status </= 2.

Exclusion Criteria:

  1. Pregnant females.
  2. Patients with colorectal cancer and K-RAS mutation will be excluded from the cetuximab arm.
  3. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
  4. 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.
  5. Patients receiving any other investigational agents.
  6. 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.
  7. Patients with history of bleeding CNS metastasis will be excluded from the trial.
  8. Hypersensitivity to any of the drugs in a particular treatment arm.
  9. Inability to complete informed consent process and adhere to protocol treatment plan and follow up requirements.
  10. History of heparin-induced thrombocytopenia.
  11. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
  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: NCT00980239

Locations
United States, Texas
University of Texas 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 M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00980239     History of Changes
Other Study ID Numbers: 2009-0410  NCI-2012-01272 
Study First Received: September 17, 2009
Last Updated: November 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Solid Tumors
Liver
hepatic arterial infusion
HAI
Bevacizumab
Avastin
Cetuximab
Erbitux
Irinotecan
Camptosar
Oxaliplatin
Eloxatin

Additional relevant MeSH terms:
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Bevacizumab
Oxaliplatin
Irinotecan
Camptothecin
Cetuximab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016