Pre-operative Administration of Anti-EGFR Monoclonal Antibodies (cetuximab) for the Eradication of Circulating Tumor Cells in Patients Undergoing Curative Treatment of Colorectal Liver Metastases; a dose finding study

Phase 2

Completed

Conditions: liver metastases
10017990
10019654

Registration Number: NL-OMON47303

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

Inclusion Criteria

- 18 years or older
- informed consent
- Presence of colorectal cancer liver metastases and patient eligible for local treatment of colorectal liver metastases
- open, laparoscopic or percutaneous treatment of liver metastases, including surgical resection radiofrequent ablation, microwave ablation, irreversible electroporation or combinations of these therapies with curative intent.
- no primary tumor in situ
- A population EGFR/EpCAM+ tumor cells (positive for epithelial markers EpCAM and EGFR) detected in the first blood sample with flow cytometry.
- Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug.

Exclusion Criteria

- Chemotherapy (< 4 weeks prior to surgery)
- Evidence of extrahepatic colorectal cancer metastases
- Prior anti-EGFR mAb therapy
- Other currently active malignancy
- Performance status > ASA 3 (American Society for Anaesthesiologists)
- Expected adverse reactions/allergies for study medication
- Mental disorder/unable to give informed consent
- Pregnancy or breast-feeding patients
- Significant skin condition interfering with treatment
- Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.
- Radiotherapy to the target lesions during study or within 4 weeks of the start of study drug.
- Major surgery within 28 days before start of study drug.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject*s participation in the study or evaluation of the study results.
- Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
- Blood transfusion during or directly after surgery

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to determine whether a single<br /><br>neoadjuvant gift of the anti-EGFR mAb cetuximab - administered 48 hours prior<br /><br>to local treatment of colorectal liver metastases - reduces the number of<br /><br>circulating tumor cells. Furthermore, we will determine the minimal effective<br /><br>dose of cetuximab to do so.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are determination of the ability of plasma from patients<br /><br>treated with cetuximab to induce growth inhibition and antibody-dependent<br /><br>phagocytosis of tumor cells. Additionally, we will determine the level of EGFR<br /><br>expression on CTCs, the immune profile, RAS mutation status and disease free<br /><br>survival. </p><br>