TACE With Irinotecan Drug-eluting Beads and Intravenous (IV) Cetuximab in Refractory Colorectal Cancer (DEBIRITUX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01060423
Recruitment Status : Terminated (Terminated due to poor subject enrolment)
First Posted : February 2, 2010
Last Update Posted : October 26, 2016
Biocompatibles UK Ltd
Information provided by (Responsible Party):
Hans-Joachim Schmoll, MD, Martin-Luther-Universität Halle-Wittenberg

Brief Summary:

The primary objective of this study is to evaluate the efficacy of Irinotecan Beads in combination with intravenous cetuximab versus intravenous irinotecan in combination with intravenous cetuximab in the treatment of patients with unresectable liver metastases from colorectal cancer.

Secondary objectives are safety and tolerability of hepatic chemoembolization and the question if the addition of aprepitant to standard antiemetic prophylaxis in patients treated by hepatic chemoembolization is safe and will reduce the rate of acute and delayed nausea and emesis.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Cetuximab Drug: Irinotecan Device: Irinotecan eluting BEADS Phase 2

Detailed Description:
About half of patients with newly diagnosed colorectal cancer will develop metastatic disease and, however, in spite of the significant progress in the therapeutical strategies for metastatic disease, virtually all patients will eventually succumb to their illness. Based on prior clinical data there is a good rationale for the expectation that the combination of systemic chemotherapy and arterial chemoembolization with drug eluting beads may be effective in the setting of patients with unresectable or chemorefractory liver metastases. The aim of this study is therefore to assess whether the combination of Irinotecan eluting beads and intravenous cetuximab is safe and effective in the treatment of patients with unresectable liver metastases from refractory colorectal cancer and will result in a prolongation of disease control when compared to standard systemic treatment with intravenous irinotecan and intravenous cetuximab. In this patient group, intravenous irinotecan plus intravenous cetuximab may represent the "standard of care", with a previously described activity. The patient group is defined in terms of pretreatment, and the scientific question is whether the way of irinotecan administration by eluting beads in feasible and somehow beneficial.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Irinotecan Drug-eluting Beads Administered by Hepatic Chemoembolization With Intravenous Cetuximab (DEBIRITUX) Versus Systemic Treatment With Intravenous Cetuximab and Irinotecan in Patients With Refractory Metastatic Colorectal Cancer and K-ras Wild-type Tumours
Study Start Date : February 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: hepatic TACE with irinotecan eluting beads and iv cetuximab
Irinotecan drug-eluting beads administered by hepatic chemoembolization with intravenous cetuximab (DEBIRITUX)
Drug: Cetuximab
Starting dose of 400mg/m2, followed by weekly 250mg/m2
Other Name: Erbitux
Device: Irinotecan eluting BEADS
A minimum of two treatments per lobe (four bi-weekly sessions in the event of bilobar disease) at week 0 and 4 with up to 4ml (100-300µm DC Bead loaded with up to 200mg irinotecan) will be scheduled (i.e. for bilobar disease right lobe: week 0, left lobe: week 2, right lobe: week 4 and left lobe: week 6: following toxicity and extending interval if toxicity seen).
Other Name: DC Bead
Active Comparator: iv cetuximab and irinotecan
systemic treatment with intravenous cetuximab and irinotecan
Drug: Cetuximab
Starting dose of 400mg/m2, followed by weekly 250mg/m2
Other Name: Erbitux
Drug: Irinotecan
Irinotecan 180 mg/m² to be administered every two weeks

Primary Outcome Measures :
  1. Progression free survival rate [ Time Frame: 6 months after first administration of study medication ]

Secondary Outcome Measures :
  1. Tumour Response (according to RECIST v1.1) [ Time Frame: every three months up to progression of disease, maximum 12 months from the date of patient enrolment ]
    extent of treated lesions

  2. Time to progression [ Time Frame: every three months, until death of patient, maximum 12 months from the date of patient enrolment ]
  3. Number of adverse events in study patients [ Time Frame: whole study, every two weeks until 28 days from the date of last administration of study medication ]
  4. Local tumour response [ Time Frame: every three months up to progression of disease, maximum 12 months from the date of patient enrolment ]
    extent of necrosis in the treated lesions

  5. Overall survival [ Time Frame: every three months, until death of patient, maximum 12 months from the date of last patient enrolment ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with confirmed diagnosis of stage IV (UICC) colorectal cancer with unresectable liver metastases (primary tumour may be present) and k-ras wild-type tumours
  2. Patients had been treated and shown to be refractory to 5-FU (Capecitabine allowed)/oxaliplatin and/or 5-FU/irinotecan. Prior therapy with VEGF-inhibitors (e.g bevacizumab) is allowed
  3. Patients with at least one measurable liver metastasis, with size > 1cm (RECIST criteria)
  4. Patients with liver only or liver dominant disease (defined as ≥ 50 % tumour burden confined to the liver)
  5. Patients with a portal vein not interfering with transarterial chemoembolization (e.g. no thrombosis) as judged by the investigator
  6. ECOG Performance status ≤ 2
  7. Life expectancy > 3 months
  8. Age ≥ 18 years.
  9. At least 4 weeks since last administration of last chemotherapy and/or radiotherapy (bone metastases may be allowed)
  10. Patients who received VEGF-inhibition (e.g. with bevacizumab) in prior therapy are eligible if stopped since 4-6 weeks before randomization
  11. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 75 x109/L
  12. INR < 1.5 (patients on therapeutic anticoagulants are not eligible)
  13. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 3 x ULN and total bilirubin ≤ 1.5 x ULN
  14. Adequate renal function: Serum creatinine ≤ 1.5 x ULN
  15. Normal level of serum magnesium
  16. Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG for women of child-bearing age
  17. Signed, written informed consent

Exclusion Criteria:

  1. Presence of CNS metastases
  2. Contraindications to irinotecan therapy (Chronic inflammatory bowel disease and/or bowel obstruction, history of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate)
  3. Active bacterial, viral or fungal infection within 72 hours of study entry
  4. Women who are pregnant or breast feeding
  5. Allergy to contrast media
  6. Presence of another concurrent malignancy. Prior malignancy in the last 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
  7. Any contraindication for hepatic embolisation procedures:

    • Large shunt as determined by the investigator (pretesting with lung perfusion scan not required)
    • Severe atheromatosis
    • Hepatofugal blood flow
  8. Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk, that would preclude the safe use of chemoembolization or would interfere with study participation
  9. Known hypersensitivity or contraindication to the drugs used in the trial (eg: cetuximab, 5-HT3 receptor antagonist, dexamethasone, or any component of aprepitant)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01060423

Zentralklinik Bad Berka GmbH, Abteilung für Interventionelle Radiologie
Bad Berka, Germany, 99437
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Germany, 01307
Kliniken Essen-Mitte, Klinik für Innere Medizin IV
Essen, Germany, 45136
Klinikum Esslingen, Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin
Esslingen, Germany, 73730
Krankenhaus Nordwest
Frankfurt/M., Germany, 60488
Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt
Frankfurt/M., Germany, 60590
Martin-Luther-Universität Halle-Wittenberg
Halle (Saale), Germany, 06097
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
SLK-Kliniken Heilbronn
Heilbronn, Germany, 74078
Otto-von-Guericke-Universität Magdeburg
Magdeburg, Germany, 39120
Universitätsklinikum Regensburg
Regensburg, Germany, 93053
Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik II
Tübingen, Germany, 72076
Universitätsklinikum Würzburg, Institut für Röntgendiagnostik
Würzburg, Germany, 97080
Sponsors and Collaborators
Hans-Joachim Schmoll, MD
Biocompatibles UK Ltd
Principal Investigator: Dirk Arnold, MD Universitätsklinikum Eppendorf, Universitäres Cancer Center

Responsible Party: Hans-Joachim Schmoll, MD, MD, Martin-Luther-Universität Halle-Wittenberg Identifier: NCT01060423     History of Changes
Other Study ID Numbers: EudraCT: 2009-014728-44
First Posted: February 2, 2010    Key Record Dates
Last Update Posted: October 26, 2016
Last Verified: October 2016

Keywords provided by Hans-Joachim Schmoll, MD, Martin-Luther-Universität Halle-Wittenberg:
liver metastasis
KRAS wildtype
irinotecan eluting beads

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action