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

• Status: Terminated
• Trial end date: 2015-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hans-Joachim Schmoll, MD
• Collaborator: Biocompatibles UK Ltd
• Treatments: Camptothecin; Cetuximab; Irinotecan

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)