Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Systemic Fluorouracil, Oxaliplatin, Leucovorin and Bevacizumab

NCT00932438 | Completed Phase 1 Results DMC

• 2 other identifiers: DEBIRI # 09.0034UL2008.1
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 10

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.

Conditions

Colon Cancer With Metastases to the Liver

Keywords

colon cancer; liver metastases

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  Tumor response will be determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Response will classified as: Complete response - disappearance of all lesions; Partial response - at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter or 30% reduction of arterial enhancement; Progressive disease - at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest longest diameter recorded since start of treatment or appearance of one or more new lesions greater than 1cm in size; Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since start of treatment.

  Months 2, 4 and 6

Secondary Outcomes (1)

• Number of Serious Adverse Events

  First treatment through one year post treatment completion

Study Arms (2)

LC Beads loaded with Irinotecan and FOLFOX6

EXPERIMENTAL

Device: LC Beads loaded with 100mg Irinotecan Drug: Systemic Chemotherapy (FOLFOX6) Oxaliplatin 85 mg/sqm, IV infusion every two weeks Leucovorin 200mg/sqm, IV infusion every two weeks 5-Fluorouracil 2400mg/sqm, IV infusion every two weeks Bevacizumab 5mg/kg given at the discretion of treating physician

Device: LC beads loaded with Irinotecan; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Bevacizumab

FOLFOX6 and Bevacizumab

ACTIVE COMPARATOR

Drug: Systemic Chemotherapy (FOLFOX6) Oxaliplatin 85 mg/sqm, IV infusion every two weeks Leucovorin 200mg/sqm, IV infusion every two weeks 5-Fluorouracil 2400mg/sqm, IV infusion every two weeks Bevacizumab 5mg/kg given at the discretion of treating physician

Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Bevacizumab

Interventions

LC beads loaded with Irinotecan DEVICE

Chemoembolization using LC beads loaded with 100mg Irinotecan

Also known as: LC Beads, TACE

LC Beads loaded with Irinotecan and FOLFOX6

Oxaliplatin DRUG

Oxaliplatin 85 mg/sqm, IV infusion every two weeks

Also known as: FOLFOX6

FOLFOX6 and Bevacizumab; LC Beads loaded with Irinotecan and FOLFOX6

Leucovorin DRUG

Leucovorin 200 mg/sqm, IV infusion every two weeks

Also known as: FOLFOX6

FOLFOX6 and Bevacizumab; LC Beads loaded with Irinotecan and FOLFOX6

5-Fluorouracil DRUG

5-Fluorouracil 2400 mg/sqm, IV infusion every 2 week

Also known as: FOLFOX6

FOLFOX6 and Bevacizumab; LC Beads loaded with Irinotecan and FOLFOX6

Bevacizumab DRUG

Bevacizumab 5 mg/kg given at the discretion of the treating physician

Also known as: Avastin

FOLFOX6 and Bevacizumab; LC Beads loaded with Irinotecan and FOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• "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

Sponsors & Collaborators

• University of Louisville: lead
• Biocompatibles UK Ltd: collaborator

Study Sites (10)

Clearview Cancer Center

Huntsville, Alabama, 35805, United States

Location

Radiology Associates of Sacramento/Sutter Cancer Center

Sacramento, California, 95816, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital/GA Cancer Specialists

Atlanta, Georgia, 30342, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Hematology and Oncology Assoc. at Bridgeport

Tupelo, Mississippi, 38801, United States

Location

Washington University/Alvin J. Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Providence Portland Medical Center/Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Oxaliplatin; Folfox protocol; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Robert Martin, Md, PhD
• Organization: University of Louisville

robert.martin@louisville.edu

602-629-3355

Study Officials

• Robert CG Martin, MD, PhD

  University of Louisville

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 3, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 11, 2021
• Results First Posted: May 7, 2021

Record last verified: 2018-03

Locations

US (9); AR (1)