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

NCT01060423 | Terminated Phase 2

• 1 other identifier: EudraCT: 2009-014728-44
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 13

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.

Conditions

Colorectal Cancer

Keywords

colorectal; liver metastasis; KRAS wildtype; chemoembolization; irinotecan eluting beads

Outcome Measures

Primary Outcomes (1)

• Progression free survival rate

  6 months after first administration of study medication

Secondary Outcomes (5)

• Tumour Response (according to RECIST v1.1)

  every three months up to progression of disease, maximum 12 months from the date of patient enrolment

• Time to progression

  every three months, until death of patient, maximum 12 months from the date of patient enrolment

• Number of adverse events in study patients

  whole study, every two weeks until 28 days from the date of last administration of study medication

• Local tumour response

  every three months up to progression of disease, maximum 12 months from the date of patient enrolment

• Overall survival

  every three months, until death of patient, maximum 12 months from the date of last patient enrolment

Study Arms (2)

hepatic TACE with irinotecan eluting beads and iv cetuximab

EXPERIMENTAL

Irinotecan drug-eluting beads administered by hepatic chemoembolization with intravenous cetuximab (DEBIRITUX)

Drug: Cetuximab; Device: Irinotecan eluting BEADS

iv cetuximab and irinotecan

ACTIVE COMPARATOR

systemic treatment with intravenous cetuximab and irinotecan

Drug: Cetuximab; Drug: Irinotecan

Interventions

Cetuximab DRUG

Starting dose of 400mg/m2, followed by weekly 250mg/m2

Also known as: Erbitux

hepatic TACE with irinotecan eluting beads and iv cetuximab; iv cetuximab and irinotecan

Irinotecan DRUG

Irinotecan 180 mg/m² to be administered every two weeks

iv cetuximab and irinotecan

Irinotecan eluting BEADS DEVICE

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).

Also known as: DC Bead

hepatic TACE with irinotecan eluting beads and iv cetuximab

Eligibility Criteria

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

You may qualify if:

• 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
• 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
• Patients with at least one measurable liver metastasis, with size \> 1cm (RECIST criteria)
• Patients with liver only or liver dominant disease (defined as ≥ 50 % tumour burden confined to the liver)
• Patients with a portal vein not interfering with transarterial chemoembolization (e.g. no thrombosis) as judged by the investigator
• ECOG Performance status ≤ 2
• Life expectancy \> 3 months
• Age ≥ 18 years.
• At least 4 weeks since last administration of last chemotherapy and/or radiotherapy (bone metastases may be allowed)
• Patients who received VEGF-inhibition (e.g. with bevacizumab) in prior therapy are eligible if stopped since 4-6 weeks before randomization
• Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 75 x109/L
• INR \< 1.5 (patients on therapeutic anticoagulants are not eligible)
• Adequate liver function as measured by serum transaminases (AST \& ALT) ≤ 3 x ULN and total bilirubin ≤ 1.5 x ULN
• Adequate renal function: Serum creatinine ≤ 1.5 x ULN
• Normal level of serum magnesium

You may not qualify if:

• Presence of CNS metastases
• Contraindications to irinotecan therapy (Chronic inflammatory bowel disease and/or bowel obstruction, history of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate)
• Active bacterial, viral or fungal infection within 72 hours of study entry
• Women who are pregnant or breast feeding
• Allergy to contrast media
• 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
• 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
• 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
• Known hypersensitivity or contraindication to the drugs used in the trial (eg: cetuximab, 5-HT3 receptor antagonist, dexamethasone, or any component of aprepitant)

Sponsors & Collaborators

• Hans-Joachim Schmoll, MD: lead
• Biocompatibles UK Ltd: collaborator

Study Sites (13)

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Dresden, 01307, Germany

Location

Zentralklinik Bad Berka GmbH, Abteilung für Interventionelle Radiologie

Bad Berka, 99437, Germany

Location

Kliniken Essen-Mitte, Klinik für Innere Medizin IV

Essen, 45136, Germany

Location

Klinikum Esslingen, Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nordwest

Frankfurt/M., 60488, Germany

Location

Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt

Frankfurt/M., 60590, Germany

Location

Martin-Luther-Universität Halle-Wittenberg

Halle, 06097, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

SLK-Kliniken Heilbronn

Heilbronn, 74078, Germany

Location

Otto-von-Guericke-Universität Magdeburg

Magdeburg, 39120, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik II

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg, Institut für Röntgendiagnostik

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Dirk Arnold, MD

  Universitätsklinikum Eppendorf, Universitäres Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 27, 2010
• First Posted: February 2, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2015
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

DE (13)