* To stratify cancer patients for participation in clinical trials.
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Percentage of screened patients with actionable genetic aberrations, defined
as genetic aberrations known to be activating in oncogenes and inactivating in
tumor suppressor genes.
Secondary outcome
* Number and nature of (serious) adverse events of the performed histological
biopsies.
* Number of samples stored for future related research.
* 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 samples at progression after initial response to targeted
treatment.
Background summary
Our knowledge on the genetic mutations in cancer is rapidly expanding and we
are increasingly testing drugs in mainly metastastic 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 objective
* To stratify cancer patients for participation in clinical trials.
Study design
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.
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, on-treatment and
post-treatment biopsies 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.
Participation in this research project contributes towards an improved efficacy
of new anti-cancer agents. Nowadays patients often face chances of less than
50% of responding to a certain treatment. We anticipate that genetic screening
will improve these odds. The patients participating in this project may already
benefit from this improvement. Certainly, future patients will benefit from
improved treatment stratification based om knowledge generated in this
project.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
1. Patients with cancer who are eligible to enter into a trial with systemic anti-cancer therapy. A CPCT-05 biopsy may be combined with a diagnostic biopsy at all instances, if deemed appropriate for selection for study participation.Exempt from biopsy: glioblastoma patients who have undergone surgery with adequate histological material available for identification of tumor specific mutations.
2. Histologic biopsy can safely be obtained:
a. Patients with safely accessible lesions according to the medical specialist performing the biopsy procedure.
b. Patients not known should not have with known bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
c. Patients must not using use any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID*s, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted. If the medical specialist performing the biopsy of a superficial lesion agrees with performing the biopsy procedure while the patient is on anticoagulant therapy other than therapeutically dosed coumarines, LMWHs and oral Xa inhibitors, the biopsy may be performed with caution.
d. Adequate hematology and coagulation status as measured by
:i. Hb > 6.0 mmol/L
Note: Red blood cell transfusions are allowed to increase the Hb.
Platelet count >100 x 109/L
ii. PT < 1.5 x ULN or PT-INR < 1.5
iii. APTT < 1.5 x ULN
iv. On the day of biopsy in patients using coumarines: PT-INR < 1.5
e. Biopsies should be performed at least four weeks after last bevacizumab administration (only in patients previously treated with bevacizumab).
3. Patients not known with contraindications for lidocaine (or its derivatives) or (in case of endoscopic guided biopsy procedure) midazolam and phentanyl.
4. Patients with adequate organ function as measured by:
a. Adequate liver function (only in case of planned liver biopsy):
i. Total bilirubin < 1.5 x ULN (except in case of documented Gilbert*s disease)
b. Adequate renal function (only in case of planned kidney biopsy):
i. Creatinine < 1.5 x ULN or
ii. Creatinine clearance (calculated by Cockroft) > 60 mL/min
5. WHO performance status 0-2
6. Patients age > 18 years, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.
Exclusion criteria
defined as positive selection criteria
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 | NCT01904916 |
| CCMO | NL45677.041.13 |