Primary objective:- To recruit patients to clinical intervention trials based on the mutational profiles of their individual cancer genome to improve treatment efficacy or intend to develop future predictors for response.Secondary objectives:- To…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of patients enrolled in clinical intervention trials based on the
mutational profile of their cancer genome
Secondary outcome
Secondary endpoints:
- Percentage of samples with sufficient DNA for sequencing analysis
- Percentage of samples with an adequate mutational profile to allow enrollment
in trials
- Database of all (anonymized) data obtained using this protocol
- Differences in mutational profile pre, post and during treatment
- Number and nature of all (serious) adverse events of the performed
histological biopsies
- Number of samples with an adequate microRNA, (phospo)proteomic profiles and
organoid cultures that allows biomarker discovery efforts. These profiles will
be deposited in the CPCT database.
- Number of filled in questionnaires, sufficient for performing e.g. health
economic analysis or PROM research.
Background summary
A major challenge for researchers in cancer care is to expedite the development
of new therapeutics. This research was set up by foundation CPCT (Centre for
Personalized Cancer Treatment) to achieve this goal. Foundation CPCT was
founded by three large cancer centers in the Netherlands: Dept. of Medical
Oncology from the University Medical Center Utrecht, Netherlands Cancer Center
- Antoni van Leeuwenhoek hospital and the Erasmus Medical Center - Cancer
institute.
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 a tumor biopsy and peripheral blood sample from all patients
included in the trial; the biopsy to obtain information on the tumor related
genetic mutations (mutational profile) and the blood sample 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 all metastatic and locally advanced 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 objective
Primary objective:
- To recruit patients to clinical intervention trials based on the mutational
profiles of their individual cancer genome to improve treatment efficacy or
intend to develop future predictors for response.
Secondary objectives:
- To determine the amount of biopsy samples with sufficient DNA for analysis
- To determine the amount of biopsy samples with an adequate mutational profile
- To collect and anonymously interpret all mutational profiles obtained using
this protocol
- To determine changes in the mutational profile under the influence of
systemic treatment
- To explore and analyze the individual microRNA,(phospho)proteomic profiles
and organoid cultures in patients with cancer to develop future predictors for
response to systemic treatment.
- To explore the correlation between mutational profiles in solid tumor
biopsies and liquid biopsies (circulating tumor DNA)
- To measure the effect of testing and treatment on the patients* motivation,
utility, QoL, productivity and informal care by means of questionnaires
Study design
This is a diagnostic study combining histological biopsy of tumor material with
DNA sequencing using the SOLiDTM 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.
The study is a Dutch multicenter study and will be executed in the hospitals as
described in C9 of this ABR form.
Study burden and risks
Burden in time of study related procedures:
- Baseline screening: approximately 3 hours
- Blood samples: approximately 5 minutes, preferably combined with other
procedures during baseline screening
- Histological biopsy: approximately 30 minutes to 4 hours (biopsy itself
approximately 15-30 minutes, afterwards observation for a maximum of 4 hours),
maximum pre-treatment and (optional and if applicable, see CPCT-02 Study
manual) post-treatment biopsies.
- Additional questionnaires for patients with pancreas cancer and FOLFIRINOX
(included >= amendment 16): approximately 30 minutes
- Additional ctDNA bloodsamples for patients with bladdercancer and
Pembrolizumab (included >= amendment 18): approximately 25 minutes (5 minutes
per bloodample: in total five additional bloodsamples will be taken)
Risks of study related procedures:
- Blood samples for pharmacogenetic analysis: small change of pain, hematoma,
infection
- Histological biopsy: small chance on pain, bleeding, infection, allergic
reaction to local anesthetic (lidocaine) or (in case of endoscopic guided
biopsy) to midazolam and/or phentanyl, tissue damage
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
* Patient with the following locally advanced or metastatic cancer for whom a
new line of therapy is indicated starting within 3 months after biopsy:
- Metastatic Pancreas Cancer: FOLFIRINOX (Folinic acid [leucovorin] +
Fluorouracil [5-FU] + Irinotecan + Oxaliplatin)
- Metastatic Bladder Cancer (including Renal Cell Cancer and all types of
Urothelial Cell Cancer): Pembrolizumab
* Measurable metastatic or locally advanced lesion(s), according to RECIST 1.1
criteria.. Guidelines for response evaluation are given in appendix A.
* Metastatic or locally advanced lesion(s) of which a histological biopsy can
safely be obtained.
* 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
No locally advanced or metastatic cancer.
Age below 18 years
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01855477 |
| CCMO | NL35781.041.11 |