Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: CPCT-02 Biopsy Protocol

Summary: 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.


Eligibility: Selection criteria, defined as inclusion criteria, are:
  1. Patients with the following locally advanced or metastatic cancer for whom a new line of therapy is indicated below starting within 3 months after biopsy:
  -  All types of malignancies: • Immunotherapy (anti-PD(L1) and/or anti-CTLA4 antibodies)
  -  VEGF targeted TKIs: Sorafenib/ Sunitinib/ Pazopanib/ Axitinib/ Cabozantinib/ Levatinib/ Regorafenib and any new VEGF targeted TKI's
  -  EGFR targeted TKIs: Erlotinib/ Gefitinib/ Afatinib Osimertinib and possibly new EGFR targeted TKI's
  -  ALK targeted TKIs: Crizotinib and any new ALK targeted TKI's
  -  BRAF and MEK targeted TKIs: Vemurafenib/ Cobimetinib/ Dabrafenib/ trametinib and any new BRAF/MEK targeted TKI's
  -  EGFR targeted antibodies: Cetuximab and Panitumumab and any new EGFR targeted antibodies.
  -  Metastatic Prostate Cancer: second generation anti hormonal therapy (Enzalutamide/ Abiraterone/ Apalutamide and any new androgen inhibitors)
  -  Metastatic ER positive Breast Cancer: anti hormonal therapy (all anti-hormonal therapies including combination with Everolimus and CDK4/6 inhibitors)
  Both standard of care treatment or treatment with these compounds within clinical trials are included. Patients with a planned inclusion in a randomized study in which the standard of care arm is a monotherapy PD1/PDL1 inhibitor are allowed, if the treatment is open-label. A CPCT-02 biopsy may be combined with a diagnostic biopsy. If a PDL-1 staining on a diagnostic biopsy is required for selection of the subsequent treatment, patient are allowed to be included in the CPCT-02 study.
  2. Measurable metastatic or locally advanced lesion(s), according to RECIST 1.1 criteria18 (or RANO criteria if applicable). For breast and prostate cancer patients with bone only disease, no measurable lesions need to be present. Patients need to have evaluable disease, bone metastases that can only be detected on bone scans without CT/MRI or serum tumor marker will be considered inevaluable. Guidelines for response evaluation are given in appendix A and C.
  3. Metastatic or locally advanced lesion(s) of which a histological biopsy can safely be obtained.
  4. Patients age > 18 years, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.
  Patients must meet selection criteria 3 not only prior to baseline biopsy, but also prior to the (optional) on-treatment and/or post-treatment biopsies.
  Exclusion criteria:
  * If one or more of the above mentioned inclusion criteria is not met

Relevance to patient case: not relevant