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

Colorectal Cancer Clinical Trial

— DEBIRITUX  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01060423
• Other study ID #: EudraCT: 2009-014728-44
• Status: Terminated
• Phase: Phase 2
• First received: January 27, 2010
• Last updated: October 25, 2016
• Start date: February 2010
• Est. completion date: May 2015

Study information

• Verified date: October 2016
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: May 2015
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ßHCG 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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Cetuximab
Starting dose of 400mg/m2, followed by weekly 250mg/m2
• Irinotecan
Irinotecan 180 mg/m² to be administered every two weeks

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).

Locations

Country	Name	City	State
Germany	Zentralklinik Bad Berka GmbH, Abteilung für Interventionelle Radiologie	Bad Berka
Germany	Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden
Germany	Kliniken Essen-Mitte, Klinik für Innere Medizin IV	Essen
Germany	Klinikum Esslingen, Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin	Esslingen
Germany	Krankenhaus Nordwest	Frankfurt/M.
Germany	Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt	Frankfurt/M.
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle (Saale)
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	SLK-Kliniken Heilbronn	Heilbronn
Germany	Otto-von-Guericke-Universität Magdeburg	Magdeburg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik II	Tübingen
Germany	Universitätsklinikum Würzburg, Institut für Röntgendiagnostik	Würzburg

Sponsors (2)

Lead Sponsor	Collaborator
Hans-Joachim Schmoll, MD	Biocompatibles UK Ltd

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival rate		6 months after first administration of study medication	No
Secondary	Tumour Response (according to RECIST v1.1)	extent of treated lesions	every three months up to progression of disease, maximum 12 months from the date of patient enrolment	No
Secondary	Time to progression		every three months, until death of patient, maximum 12 months from the date of patient enrolment	No
Secondary	Number of adverse events in study patients		whole study, every two weeks until 28 days from the date of last administration of study medication	Yes
Secondary	Local tumour response	extent of necrosis in the treated lesions	every three months up to progression of disease, maximum 12 months from the date of patient enrolment	No
Secondary	Overall survival		every three months, until death of patient, maximum 12 months from the date of last patient enrolment	No