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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00980239
First received: September 17, 2009
Last updated: February 12, 2014
Last verified: February 2014
  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: Single Group 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 ]
  • Dose-limiting toxicities (DLTs) [ Time Frame: Evaulated with each 28 day cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 140
Study Start Date: September 2009
Estimated Primary Completion Date: September 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

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 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. 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, 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
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: NCT00980239     History of Changes
Other Study ID Numbers: 2009-0410, NCI-2012-01272
Study First Received: September 17, 2009
Last Updated: February 12, 2014
Health Authority: United States: Institutional Review Board

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:
Liver Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antibodies, Monoclonal
Oxaliplatin
Irinotecan
Bevacizumab
Cetuximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014