Clinical trial NCT01060423: TACE With Irinotecan Drug-eluting Beads and Intravenous (IV) Cetuximab in Refractory Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: colorectal
liver metastasis
KRAS wildtype
chemoembolization
irinotecan eluting beads
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
Collaborators: name: Biocompatibles UK Ltd
First posted: 2010-02-02
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression free survival rate
timeFrame: 6 months after first administration of study medication
Secondary outcomes:
measure: Tumour Response (according to RECIST v1.1)
timeFrame: every three months up to progression of disease, maximum 12 months from the date of patient enrolment
measure: Time to progression
timeFrame: every three months, until death of patient, maximum 12 months from the date of patient enrolment
measure: Number of adverse events in study patients
timeFrame: whole study, every two weeks until 28 days from the date of last administration of study medication
measure: Local tumour response
timeFrame: every three months up to progression of disease, maximum 12 months from the date of patient enrolment
measure: Overall survival
timeFrame: every three months, until death of patient, maximum 12 months from the date of last patient enrolment
Other outcomes:
Locations:
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH, Abteilung für Interventionelle Radiologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Klinik für Innere Medizin IV
city: Esslingen
country: Germany
facility: Klinikum Esslingen, Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin
city: Frankfurt/M.
country: Germany
facility: Krankenhaus Nordwest
city: Frankfurt/M.
country: Germany
facility: Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt
city: Halle (Saale)
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-Universität Magdeburg
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik II
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Institut für Röntgendiagnostik
Study officials:
affiliation: Universitätsklinikum Eppendorf, Universitäres Cancer Center
name: Dirk Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References: