Treatment Optimization of Cetuximab in Patients With Metastatic Colorectal Cancer Based on Tumor Uptake of 89Zr-labeled Cetuximab Assessed by PET
|ClinicalTrials.gov Identifier: NCT01691391|
Recruitment Status : Completed
First Posted : September 24, 2012
Last Update Posted : March 21, 2017
3rd line standard treatment of patients with metastatic colorectal cancer (CRC) harboring K-ras wild type consists of anti-EGFR treatment with either cetuximab or panitumumab. This type of treatment has a modest but significant beneficial activity in this patient group with improved progression-free and overall survival. Although it is well known that patients with advanced CRC harboring a K-Ras mutation will not respond to anti-EGFR treatment, it is not understood why patients with K-Ras wild type CRC do not all benefit from this type of therapy. In order to optimize treatment of these patients as well as health care costs, it is extremely important to identify those patients who will respond to treatment with an EGFR inhibitor at an early stage.
The investigators hypothesize that the differences in response to treatment with cetuximab are due to variability in the pharmacokinetics and -dynamics of the antibody. Thus, the investigators hypothesize that patients who do not respond to anti-EGFR treatment, have insufficient drug levels in tumor tissue. The investigators hypothesize that this is due to pharmacodynamic processes such as sequestration of cetuximab in the liver which expresses high levels of EGF receptor.
With the introduction of immuno-positron emission tomography (PET), an attractive novel option to visualize molecular interactions has been developed using the combination of PET with labeled mAbs. Cetuximab labeled with zirconium-89 (89Zr) has been successfully generated (GMP) and is available for this study. Previous studies have shown excellent stability of this compound and 89Zr is shown to be safe in humans. The investigators will use 89Zr-cetuximab to demonstrate tumor targeting by imaging and explore the relation of uptake with treatment response. With this approach the investigators hope to achieve a better understanding of the mechanisms of action of this therapeutic mAb in metastasized CRC and eventually develop strategies that may improve efficacy of cetuximab treatment.
|Condition or disease||Intervention/treatment|
|Colorectal Cancer||Behavioral: pharmacodynamic purposes of 89Zr-labelled cetuximab and kinase activity profiles|
|Study Type :||Observational|
|Actual Enrollment :||11 participants|
|Official Title:||Treatment Optimization of Cetuximab in Patients With Metastatic Colorectal Cancer Based on Tumor Uptake of 89Zr-labeled Cetuximab Assessed by PET|
|Study Start Date :||January 2012|
|Primary Completion Date :||January 2015|
|Study Completion Date :||July 2016|
Advanced CRC, candidates for anti-EGFR antibody monotherapy
Patients with histopathologically confirmed advanced CRC with K-Ras wild type, aged ≥ 18 years, with a life expectancy of at least 12 weeks, who are candidates for anti-EGFR antibody monotherapy (3rd line palliative treatment).
Behavioral: pharmacodynamic purposes of 89Zr-labelled cetuximab and kinase activity profiles
Patients will be treated with cetuximab. For pharmacodynamic purposes PET-imaging with 89Zr-labelled cetuximab will be performed. In addition, two [18F-]-FDG PET-CT will be performed to explore early response. Patients will undergo blood sampling and two skin biopsies for pharmacodynamic purposes of 89Zr-labelled cetuximab and kinase activity profiles, respectively.
- The detection of 89Zr-cetuximab uptake in non-hepatic tumor lesions [ Time Frame: At 0-2h, day 2,3,4 and 7 after administration of 89Zr -cetuximab ]The detection of 89Zr-cetuximab uptake in non-hepatic tumor lesions (present/absent; present being defined as levels measured in ROI's > standard deviation of background +1).
- The % uptake (of total injected) 89Zr-cetuximab in non-hepatic tumor lesions [ Time Frame: At 0-2h, day 2,3,4 and 7 after administration of 89Zr -cetuximab ]The % uptake (of total injected) 89Zr-cetuximab in non-hepatic tumor lesions as measured in ROI's corrected for background levels.
- The % uptake (of total injected) 89Zr-cetuximab in liver lesions [ Time Frame: At 0-2h, day 2,3,4 and 7 after administration of 89Zr -cetuximab ]The % uptake (of total injected) 89Zr-cetuximab in liver lesions as measured in ROI's corrected for background levels.
- [18F-]FDG PET measurements [ Time Frame: 4 weeks before start and 4 weeks after start ][18F-]FDG PET measurements (SUVmax) before and after 4 weeks of treatment with cetuximab.
- Grade of skin toxicity [ Time Frame: every 4 weeks until progressive disease ]Grade of skin toxicity as measured by predefined criteria (see below).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01691391
|VU University Medical Center|
|Amsterdam, Noord Holland, Netherlands, 1081 HV|