Clinical trial NCT01855477: CPCT-02 Biopsy Protocol
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Solid Tumors
Metastatic Disease
Lead sponsor: Foundation CPCT
Sponsor class: OTHER
Collaborators: name: Hartwig Medical Foundation
First posted: 2013-05-16
Enrollment: 6927
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: • Percentage of patients enrolled in clinical intervention trials based on the mutational profile of their cancer genome
timeFrame: 3 months after baseline biopsy
Secondary outcomes:
measure: Percentage of samples with sufficient DNA for sequencing analysis
timeFrame: 1 year after baseline biopsy
measure: • Percentage of samples with an adequate mutational profile to allow enrollment in trials
timeFrame: 1 year after baseline biopsy
measure: Differences in mutational profile pre, post and during treatment
timeFrame: 1 year after last biopsy within one line of treatment
measure: • Number and nature of (serious) adverse events of the performed histological biopsies
timeFrame: 14 days after each biopsy procedure
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Foundation CPCT, Radboud UMC
state: Zuid-holland
Study officials:
affiliation: Radboud University Medical Center
name: Haiko HJ Bloemendal, Prof. Dr.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.