CPCT-02 Biopsy Protocol

Study Overview
=================
Brief 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.

Official Title
-----------------
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)

Conditions
-----------------
Solid Tumors, Metastatic Disease

Intervention / Treatment
-----------------
* Procedure: Histological biopsy procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
Selection criteria, defined as inclusion criteria, are: 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 (see also table 2): - Metastatic Pancreas Cancer: FOLFIRINOX (Folinic acid [leucovorin] + Fluorouracil [5-FU] + Irinotecan + Oxaliplatin) Measurable metastatic or locally advanced lesion(s), according to RECIST 1.1 criteria18. Guidelines for response evaluation are given in appendix A. Metastatic or locally advanced lesion(s) of which a histological biopsy can safely be obtained. 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 and if applicable, see CPCT-02 Study manual) post-treatment biopsies. Exclusion criteria: * If one or more of the above mentioned inclusion criteria is not met

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Histological biopsy procedure<br>This is a multicenter study combining histological biopsy of tumor material with DNA sequencing using Next Generation Sequencing (NGS) platform. The study aims to obtain a more accurate pre-treatment stratification of cancer patients by obtaining fresh tumor biopsies for next-generation sequencing to obtain a mutational profile. | Procedure: Histological biopsy procedure<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Percentage of patients enrolled in clinical intervention trials based on the mutational profile of their cancer genome |  | 3 months after baseline biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of samples with sufficient DNA for sequencing analysis |  | 1 year after baseline biopsy | 
| • Percentage of samples with an adequate mutational profile to allow enrollment in trials |  | 1 year after baseline biopsy | 
| Differences in mutational profile pre, post and during treatment |  | 1 year after last biopsy within one line of treatment | 
| • Number and nature of (serious) adverse events of the performed histological biopsies |  | 14 days after each biopsy procedure |