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

University of Louisville (UOFL)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Colon Cancer With Metastases to the Liver

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00932438

DEBIRI # 09.0034

UL2008.1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

LC Beads loaded with Irinotecan and FOLFOX6

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Oxaliplatin

Drug: 5-Fluorouracil

Device: LC beads loaded with Irinotecan

Drug: Leucovorin

FOLFOX6 and Bevacizumab

Active Comparator group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Oxaliplatin

Drug: 5-Fluorouracil

Drug: Leucovorin