CPCT-05 Biopsy Protocol Patient Selection

Study Overview
=================
Brief Summary
-----------------
Our knowledge on the genetic mutations in cancer is rapidly expanding and we are increasingly testing drugs in mainly metastatic cancer patient populations with rare mutations. Successful examples of this new strategy are ALK inhibitors in ALK translocated NSCLC (less than 5% frequency) and EGFR inhibitors in EGFR mutant NSCLC (approximately 5% frequency). Selecting molecularly stratified patient populations for studies benefits the patient as it increases the odds of obtaining benefit from experimental treatment, especially in early clinical trials. Moreover it increases the speed and efficacy of drug development as signs of efficacy are picked up in earlier phases. Therefore, broad screening of molecular lesions in the tumors of patients that are being considered for participation in trials is crucial. This pre-selection increases our ability to perform several trials in parallel and thus include more patients in more meaningful trials. With the still dismal prognosis of patients with metastatic cancer, increasing the accrual rate to pivotal trials in selected patient populations is a key factor in improving prognosis. The advent of Next Generation Sequencing (NGS) platforms enables us to probe a limited number of cancer related genes within 2-4 weeks. We have extensively piloted this approach and are now able to deliver clinically meaningful turn-around-times. This development enables us to use this technology to enrich clinical trials using targeted therapies for patients with specific mutations. We will obtain tumor biopsies of a metastatic or locally advanced lesion and a 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 and our own experience show that tumor biopsies can be performed with only minor complications and acceptable risks. We will recruit patients with metastatic or locally advanced solid tumors from patients that can potentially be included in clinical trials.

Official Title
-----------------
Protocol to Obtain Tumor Biopsies From Patients With Locally Advanced (Incurable) or Metastatic Cancer to Improve Selection for Clinical Trials. (CPCT - 05 Biopsy Protocol Patient Selection)

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Locally advanced (incurable) or metastatic cancer from a histological or cytological proven solid tumor Indication for systemic treatment with anti-cancer agents (with no treatment options with curative intent) Measurable locally advanced (incurable) or metastatic lesion(s), according to RECIST 1.1 criteria. Safe biopsy of a metastatic or locally advanced lesion possible No contraindications for lidocaine (or its derivatives) and/or midazolam and/or phentanyl Adequate organ function WHO performance status 0-2 Age > 18 yr Expected adequacy to follow up Written informed consent 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 diagnostic multicenter study combining histological biopsy of tumor material with DNA sequencing using Ion Torrent®, Next Generation Sequencing (NGS) platform. The study aims improve stratification of cancer patients by obtaining fresh tumor biopsies for next-generation sequencing for participation in clinical trials. | Procedure: Histological biopsy procedure<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of screened patients allocated to trials based upon outcome of genetic screening effort. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and nature of (serious) adverse events of the performed histological biopsies. |  | 2 days after each biopsy procedure | 
| Number of samples stored for future related research. |  | 1 year | 
| Number of samples with an adequate microRNA, (phospho)proteomic profiles and organoid cultures that allows biomarker discovery efforts. These profiles will be deposited in the CPCT database. |  | 1 year |