MedTrace Logo

Early Biomarker With 18F-FDG PET for Treatment Optimization of Anti-EGFR Therapy in Patients With Metastatic Colorectal Cancer.

NCT01691391 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 46

Last updated 2020-11-04

No results posted yet for this study

Summary

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.

The phase I part of the study was fulfilled after inclusion of 36 patients to evaluate the potential applicability of the 89Zr-cetuximab PET as predictive marker for (absence of) response to cetuximab. Along with this analysis, FDG-PET evaluation before and after 1 administration of cetuximab was being performed. While we observed no correlation of 89Zr-cetuximab tumor uptake with clinical benefit in these 36 patients, we did find a clinical significant predictive value for the absence of response with early 18F-FDG-PET with the lack of clinical benefit at 2 months of treatment in this group of patients. Early 18F-FDG PET response evaluation shows great potential to be a clinically applicable tool to stop an ineffective treatment in a very early phase after one administration of treatment. Such an early predictor is unprecedented in clinical daily practice and will 1) avoid unnecessary toxicity of inactive treatment, 2) will lead to faster prescription of a potentially active alternative treatment and 3) will reduce costs by preventing administration of inactive treatment. In order to provide solid evidence for this new approach, we aim to validate early 18F-FDG-PET as a predictive imaging strategy to identify non-responders in part 2 of the study.

Conditions

Interventions

BEHAVIORAL

(Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profiles

Patients will be treated with cetuximab or panitumumab. Two \[18F-\]-FDG PET-CT will be performed to explore early response. Patients will undergo blood sampling and two skin and tumor biopsies for kinase activity profiles.

Sponsors & Collaborators

  • Radboud University Medical Center

    collaborator OTHER

  • Jeroen Bosch Ziekenhuis

    collaborator OTHER

  • Leiden University Medical Center

    collaborator OTHER

  • NKI-AvL

    collaborator UNKNOWN

  • Academisch Ziekenhuis Groningen

    collaborator OTHER

  • Amsterdam UMC, location VUmc

    lead OTHER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2012-01-31
Primary Completion
2020-11-03
Completion
2020-11-03

Countries

  • Netherlands

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01691391 on ClinicalTrials.gov