CPCT-02 Biopsy Protocol (CPCT-02)

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)

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 6927
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-holland
    • Nijmegen, Zuid-holland, Netherlands, 6500 HB
      • Foundation CPCT, Radboud UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (see also table 2):

   - Metastatic Pancreas Cancer: FOLFIRINOX (Folinic acid [leucovorin] + Fluorouracil [5-FU] + Irinotecan + Oxaliplatin)

2. Measurable metastatic or locally advanced lesion(s), according to RECIST 1.1 criteria18. Guidelines for response evaluation are given in appendix A.
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 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

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 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Foundation CPCT
• Collaborators: Hartwig Medical Foundation
• Investigators: Study Director: Haiko HJ Bloemendal, Prof. Dr., Radboud University Medical Center

Publications and helpful links

General Publications

• Nakauma-Gonzalez JA, Rijnders M, van Riet J, van der Heijden MS, Voortman J, Cuppen E, Mehra N, van Wilpe S, Oosting SF, Rijstenberg LL, Westgeest HM, Zwarthoff EC, de Wit R, van der Veldt AAM, van de Werken HJG, Lolkema MPJ, Boormans JL. Comprehensive Molecular Characterization Reveals Genomic and Transcriptomic Subtypes of Metastatic Urothelial Carcinoma. Eur Urol. 2022 Apr;81(4):331-336. doi: 10.1016/j.eururo.2022.01.026. Epub 2022 Jan 25.
• Roepman P, de Bruijn E, van Lieshout S, Schoenmaker L, Boelens MC, Dubbink HJ, Geurts-Giele WRR, Groenendijk FH, Huibers MMH, Kranendonk MEG, Roemer MGM, Samsom KG, Steehouwer M, de Leng WWJ, Hoischen A, Ylstra B, Monkhorst K, van der Hoeven JJM, Cuppen E. Clinical Validation of Whole Genome Sequencing for Cancer Diagnostics. J Mol Diagn. 2021 Jul;23(7):816-833. doi: 10.1016/j.jmoldx.2021.04.011. Epub 2021 May 6.
• Mendelaar PAJ, Smid M, van Riet J, Angus L, Labots M, Steeghs N, Hendriks MP, Cirkel GA, van Rooijen JM, Ten Tije AJ, Lolkema MP, Cuppen E, Sleijfer S, Martens JWM, Wilting SM. Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features. Nat Commun. 2021 Jan 25;12(1):574. doi: 10.1038/s41467-020-20887-6. Erratum In: Nat Commun. 2021 May 26;12(1):3269. doi: 10.1038/s41467-021-23629-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2011
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: May 13, 2013
• First Posted (Estimated): May 16, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: NL35781.041.11