CPCT-05 Biopsy Protocol Patient Selection

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)

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors; Metastatic Disease
• Intervention / Treatment: Procedure: Histological biopsy procedure

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Utrecht, Netherlands, 3508 GX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Procedure: Histological biopsy procedure

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: P.O. Witteveen
• Collaborators: Erasmus Medical Center; The Netherlands Cancer Institute
• Investigators: Principal Investigator: Marlies Langenberg, MD, PhD, UMC Utrecht; Principal Investigator: Neeltje Steeghs, MD, PhD, Antoni van Leeuwenhoek Hospital; Principal Investigator: Maja J.A. de Jonge, MD, PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: NL.45677.041.13