Development of a Platform for Next-generation DNA Sequencing Based Personalized Treatment for Cancer Patients: Protocol to Obtain Biopsies From Patients With Locally Advanced or Metastatic Cancer (CPCT - 02 Biopsy Protocol)

A major challenge for researchers in cancer care is to expedite the development of new therapeutics and the Center for Personalized Cancer Treatment (a collaboration of the Dept. of Medical Oncology from the University Medical Center Utrecht, Netherlands Cancer Center - Antoni van Leeuwenhoek hospital and the Erasmus Medical Center - Daniël den Hoed clinic) is an initiative to achieve this goal.

The current and future generation anti-cancer drugs are developed to specifically activate or deactivate deregulated gene products or signaling pathways in cancer cells. The development of such "targeted" agents is an exciting new opportunity that promises to deliver more anti-cancer efficacy and less toxicity. Although targeted therapy has been a breakthrough in medical oncology leading to the development of a portfolio of potentially successful new drugs, it has not yet delivered the much needed relief for large patient populations. We believe that the development of these agents is mainly hampered by our lack of successful patient selection.

The CPCT aims to select patients for clinical trial participation based on the results of Next Generation Sequencing (NGS) information obtained from tumor material. The advent of NGS platforms enables us to probe a significant proportion of the cancer genome and thus to develop a realistic view on the complex genetic changes in cancer cells. The CPCT aims to use NGS platforms to improve the selection of patients for targeted therapy trials.

We will obtain tumor biopsies of a (preferably) metastatic or locally advanced lesion and peripheral blood sample from all patients included in the trial; the biopsies to obtain information on the tumor related genetic mutations (mutational profile) and the blood samples to assess each patient's germline DNA background variation. As patients will be asked to undergo an invasive procedure it is important to address the potential safety issues. Review of the literature shows that in general tumor biopsies can be performed with only minor complications and acceptable risks. We will recruit patients with metastatic or locally advanced (incurable) solid tumors and we aim to use the information obtained from DNA sequencing to stratify patients for inclusion in clinical trials. The final personalized treatment decision will be made dependent on the availability of trials and the expected predictive value of the mutational profile.