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

NCT ID: NCT00932438

Last Updated: 2021-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2012-12-31

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.

Conditions

Colon Cancer With Metastases to the Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LC Beads loaded with Irinotecan and FOLFOX6

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

Group Type: EXPERIMENTAL

LC beads loaded with Irinotecan

Intervention Type: DEVICE

Chemoembolization using LC beads loaded with 100mg Irinotecan

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 85 mg/sqm, IV infusion every two weeks

Leucovorin

Intervention Type: DRUG

Leucovorin 200 mg/sqm, IV infusion every two weeks

5-Fluorouracil

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: DRUG

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

FOLFOX6 and Bevacizumab

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

Group Type: ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 85 mg/sqm, IV infusion every two weeks

Leucovorin

Intervention Type: DRUG

Leucovorin 200 mg/sqm, IV infusion every two weeks

5-Fluorouracil

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: DRUG

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

Interventions

LC beads loaded with Irinotecan

Chemoembolization using LC beads loaded with 100mg Irinotecan

Intervention Type: DEVICE

Oxaliplatin

Oxaliplatin 85 mg/sqm, IV infusion every two weeks

Intervention Type: DRUG

Leucovorin

Leucovorin 200 mg/sqm, IV infusion every two weeks

Intervention Type: DRUG

5-Fluorouracil

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

Intervention Type: DRUG

Bevacizumab

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

Intervention Type: DRUG

Other Intervention Names

LC Beads, TACE; FOLFOX6; FOLFOX6; FOLFOX6; Avastin

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biocompatibles UK Ltd

INDUSTRY

Sponsor Role: collaborator

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Robert C. Martin

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert CG Martin, MD, PhD

Role: STUDY_DIRECTOR

University of Louisville

Locations

Clearview Cancer Center

Huntsville, Alabama, United States

Radiology Associates of Sacramento/Sutter Cancer Center

Sacramento, California, United States

Emory University

Atlanta, Georgia, United States

Northside Hospital/GA Cancer Specialists

Atlanta, Georgia, United States

University of Louisville

Louisville, Kentucky, United States

Hematology and Oncology Assoc. at Bridgeport

Tupelo, Mississippi, United States

Washington University/Alvin J. Siteman Cancer Center

St Louis, Missouri, United States

Providence Portland Medical Center/Providence Cancer Center

Portland, Oregon, United States

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Countries

United States; Argentina

Other Identifiers

UL2008.1

Identifier Type: -

Identifier Source: secondary_id

DEBIRI # 09.0034

Identifier Type: -

Identifier Source: org_study_id