The main objective of this pilot study is to determine intratumoral concentrations of kinase inhibitors upon 2 weeks of treatment in tumor tissue of patients.
ID
Source
Brief title
Condition
- Other condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Health condition
alle vormen van gevorderde, dwz inoperabele of uitgezaaide, solide tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine intratumoral kinase inhibitor concentrations upon 2 weeks of
treatment.
Secondary outcome
To determine kinase inhibitor concentrations in plasma, serum and PBMC's upon 2
weeks of treatment.
To determine intra-dermal kinase inhibitor concentrations upon 2 weeks of
treatment.
To determine per patient whether 2 weeks of treatment with kinase inhibitors
induces significant change of (1) phosphoproteomic profiles in tumor tissue;
(2) kinase activity in tumor tissue; (3) markers for antiangiogenic and
antiproliferative activity in tumor tissue; (4) serum peptide profiles
Background summary
In the past decade multiple agents targeting specific signaling proteins
important for tumor growth and angiogenesis, including (tyrosine) kinase
inhibitors and monoclonal antibodies, have been developed and have reached
clinical approval. Thus far, it is unclear which patients will respond to these
agents and why targeted agents are only effective in a small subgroup of cancer
patients. Clinically applicable diagnostic tools to predict whether a patient
will respond to targeted agents are not yet available. It is assumed that
responses to these agents depend on specific receptor and protein signaling
activities in tumor tissues. Our general hypothesis is that (phospho)proteomic
and kinase activity profiling in tissue before and during treatment with kinase
inhibitors may provide more insight in which markers can be clinically used to
predict response to this type of targeted therapy.
We hypothesize that intratumoral drug concentrations will provide the most
reliable and relevant data when used in in vitro assays to determine changes of
(phospho)proteomic and kinase activity profiles in tumor tissue. To date,
literature on intratumoral kinase inhibitor concentrations is not available.
Results of this pilot study will be used for the design of a study aimed at
determining biological and early clinical response in tumor tissue upon 2 weeks
of treatment with kinase inhibitors.
Study objective
The main objective of this pilot study is to determine intratumoral
concentrations of kinase inhibitors upon 2 weeks of treatment in tumor tissue
of patients.
Study design
Single center, non-randomized interventional pilot study.
Intervention
Patients will be cohort-wise treated with clinically available kinase
inhibitors for 2 weeks prior to standard palliative treatment. Five patients
will be included in each of seven drug cohorts. Biopsies will be performed to
determine intratumoral drug concentrations and to compare tissue
(phospho)proteomic and kinase activity profiles before and during therapy.
Study burden and risks
Enrolment in this study will require 2 weeks of treatment with a clinically
approved kinase inhibitor prior to standard palliative treatment. As much as
possible, we aim to include patients who will receive standard treatment with
one of the study kinase inhibitors. However, not all study drugs are
administered as monotherapy standardly. Adverse events as a result of the
kinase inhibitor treatment may occur. A tumor biopsy prior to and during
treatment will be taken. This biopsy may cause physical discomfort. During
therapy, follow-up until start of palliative treatment will include laboratory
analysis on a visit to the outpatient clinic. Before starting standard
palliative treatment, potential antitumor activity of two weeks kinase
inhibitor treatment can not be ruled out. Results of this study will be used
for personalized treatment selection strategies that may prevent unnecessary
toxicity of ineffective therapy in the future.
De Boelelaan 1117
1081 HV Amsterdam
NL
De Boelelaan 1117
1081 HV Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Advanced solid malignancy, minimum age 18 years, indication for palliative treatment, measurable disease with at least one lesion accessable for biopsy
Exclusion criteria
Cardiovascular conditions including congestive heartfailure NYHA class >2, recent myocardial infarction or uncontrolled coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy, uncontrolled hypertension; uncontrolled infections; serious non-healing wound, ulcer or bone fracture, pregnant or breast feeding.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2011-000219-21-NL |
| CCMO | NL35441.029.11 |