CPCT-05 Biopsy Protocol Patient Selection

Not Applicable

Terminated

• Conditions: Metastatic Disease; Solid Tumors
• Interventions: Procedure: Histological biopsy procedure

• Registration Number: NCT01904916
• Lead Sponsor: P.O. Witteveen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-17
• Study First Submitted QC: 2013-07-17
• Study First Posted: 2013-07-22
• Study Start: 2014-01
• Primary Completion: 2016-01
• Study Completion: 2017-03
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-07
• Last Update Posted: 2018-03-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 195

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Histological biopsy procedure	Histological biopsy procedure	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.

Primary Outcome Measures

Name	Time	Method
Percentage of screened patients allocated to trials based upon outcome of genetic screening effort.	1 year

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

Antoni van Leeuwenhoek Ziekenhuis; 🇳🇱 Amsterdam, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands