Clinical trial NCT00932438: Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Systemic Fluorouracil, Oxaliplatin, Leucovorin and Bevacizumab
Official title: Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Concomitant Systemic Oxaliplatin, Fluorouracil and Leucovorin Chemotherapy, and Anti-Angiogenic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colon Cancer With Metastases to the Liver
Keywords: colon cancer
liver metastases
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: Biocompatibles UK Ltd
First posted: 2009-07-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicentre, open labeled, controlled phase study designed to assess effectiveness of chemoembolization with LC Beads, both with and without systemic chemotherapy, in the treatment of unresectable liver metastases in patients with colorectal cancer.

Detailed description: This is a multicentre, open labeled, prospective, randomized, controlled phase I/II study designed to assess the clinical performance of chemoembolization with Low Compression Bead (LC Bead), loaded with irinotecan in combination with intravenous chemotherapy and bevacizumab versus intravenous chemotherapy in combination with bevacizumab in the treatment of unresectable liver metastases in patients with colorectal cancer.

Eligibility criteria: Inclusion:

* Patients over 18 years of age, of any race or sex, who have histologic or radiologic proof of colorectal cancer to the liver, who are able to give informed consent, will be eligible.
* Patients with at least one measurable liver metastases, with size \> 1cm response evaluation criteria in solid tumors (RECIST)
* Patients with liver dominant disease defined as ≥80% tumor body burden confined to the liver
* Patients with patent main portal vein
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of \< 2
* Life expectancy of \> 3 months
* Non-pregnant with an acceptable contraception in premenopausal women.
* Hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥75 x109/L, international normalized ratio (INR) ≤1.3\* (\*If patient is on anticoagulants, they must be able to stop medication temporarily prior to TACE and must have INR ≤1.3 prior to receiving TACE) Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤5 times upper limits of normal (ULN), albumin ≥2.5g/dl, Adequate Hemoglobin and Hematocrit as measured by (Male: for approximate 45 - 62%; and approximate Female: 37 - 48%) or Hemoglobin (Male: approximate 13 - 18 gm/dL Female: approximate 12 - 16 gm/dL). If patient is asymptomatic with Hemoglobin for male 10 to 12.9 or Female 9.5 to 11.9 and do not wish to be transfused they still will be eligible for treatment.
* Adequate renal function (creatinine ≤ 2.0mg/dl)
* Women of child bearing potential and fertile men are required to use effective contraception negative serum beta human chorionic gonadotropin (βHCG)
* Signed, written informed consent
* Patient is at least one month out from any treatment for Stage III colorectal cancer
* Patient is at least one year out from any treatment for their Stage IV colorectal cancer.

  - these patients should not be candidates for curative treatments, and will have recovered from any chemotherapeutic toxicities' they may have experienced."
* Less than 60% liver tumor replacement

Exclusion:

* "Any patient eligible for curative treatment (i.e. resection or radiofrequency ablation). Note: resectability is defined as a single tumor \<5cm with adequate liver function defined: Total bilirubin ≤ 2.0mg/dl" non-resectability includes patients with greater than 6, tumors close to blood vessels, patients with hepatic-pulmonary shunting, or patients of poor performance"
* Active bacterial, viral or fungal infection within 72 hours of study entry
* Women who are pregnant or breast feeding
* Allergy to contrast media that cannot be managed with standard care (e.g. steroids), making magnetic resonance imaging (MRI) or computed tomography (CT) contraindicated.
* Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous carcinoma of the skin.
* Any contraindication for hepatic embolization procedures:

  * Large shunt as determined by the investigator (pretesting with TcMMA not required)
  * Severe atheromatosis
  * Hepatofugal blood flow
  * Main portal vein occlusion (e.g. thrombus or tumor)
* Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk and that would preclude the safe use of chemoembolization or would interfere with study participation
* Patients with prior contraindications for the use of irinotecan therapy-this would include chronic inflammatory bowel disease and or bowel obstruction, history of severe hypersensitivity reactions to irinotecan hydrochloride, trihydrate, lactic acid or to any of the excipients of camptosar, severe bone marrow failure, history of Gilbert Syndrome or concomitant use with St. John's Wort
* Patients with prior contraindications for the use of fluorouracil, oxaliplatin, leucovorin or bevacizumab

Primary outcomes:
measure: Tumor Response
timeFrame: Months 2, 4 and 6
Secondary outcomes:
measure: Number of Serious Adverse Events
timeFrame: First treatment through one year post treatment completion
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Center
state: Alabama
city: Sacramento
country: United States
facility: Radiology Associates of Sacramento/Sutter Cancer Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital/GA Cancer Specialists
state: Georgia
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Tupelo
country: United States
facility: Hematology and Oncology Assoc. at Bridgeport
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University/Alvin J. Siteman Cancer Center
state: Missouri
city: Portland
country: United States
facility: Providence Portland Medical Center/Providence Cancer Center
state: Oregon
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
Study officials:
affiliation: University of Louisville
name: Robert CG Martin, MD, PhD
role: STUDY_DIRECTOR
References: