This study has two primary objectives:To determine the effect of taxane therapy on the release of bone marrow derived endothelial progenitor cells.To study the effect of bevacizumab on taxane induced release of bone marrow derived endothelial…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To clarify the mechanism of the occurrence of the endothelial progenitor cell
burst that occurs after chemotherapy by :
Determining the effect of taxane therapy on the release of bone marrow derived
progenitor endothelial cells.
Studying the effect of bevacizumab on taxane induced release of bone marrow
derived progenitor endothelial cells
Secondary outcome
To explore whether there is a difference in progenitor cell dynamics between
paclitaxel and docetaxel and a weekly or threeweekly regimen.
To determine whether anti-angiogenic treatment affect platelet biology by
testing:
1) Whether anti-angiogenic treatment impairs the angiogenic activity of
isolated platelets from patients receiving bevacizumab treatment by using an
endothelial cell proliferation assay as a potential biomarker for bevacizumab
activity.
2) Whether platelets markers of activation can be detected in platelet samples
or plasma from patients receiving bevacizumab treatment.
3) Whether platelet function is changed in aggregation and activation studies
in vitro of isolated platelets from patients receiving bevacizumab treatment.
Background summary
Recent findings have demonstrated that taxanes (and perhaps several other
chemotherapeutics) induce an immediate release of bone marrow progenitor
endothelial cells. This release occurs within hours after administering
chemotherapy to the patient. The clinical relevance of the release of bone
marrow derived cells is currently unclear. In preclinical tumor models
perturbation of the tumor with a vascular disrupting agent induces a similar
release which coincides with rapid re-growth of the tumor. In addition,
preliminary preclinical experiments suggest that bevacizumab may prevent the
release of bone marrow derived endothelial cells. We have also found that
platelets take up bevacizumab which subsequently neutralizes VEGF stored in the
alpha granules. Blockade of platelet VEGF may reduce their normal angiogenic
potential. Reduction of their angiogenic potential can be measured in
endothelial cell proliferation assays and may be used as a potential biomarker
for bevacizumab activity. Since platelets are important in wound healing and
coagulation, impaired platelet function may also have adverse effects in
patients treated with bevacizumab. For example, bowel perforations may be
explained by this mechanism. There are no studies specifically addressing this
question.
Study objective
This study has two primary objectives:
To determine the effect of taxane therapy on the release of bone marrow derived
endothelial progenitor cells.
To study the effect of bevacizumab on taxane induced release of bone marrow
derived endothelial progenitor cells
Secondary objectives are:
To determine the type of taxane and schedule on the release of bone marrow
derived endothelial cells.
To determine the effect of bevacizumab monotherapy and in combination with
taxane chemotherapy on platelet biology and angiogenic growth factors
Study design
A translational study in which primary endpoint is concerning biomarker
dynamics and not efficacy or safety of the drugs being administrated.
This study is designed as a two step translational study in which we study in
part A in the first 2 cohorts of 12 patients whether docetaxel and paclitaxel
in most frequently used clinical dosing regimens induce a release of progenitor
cells from the bone marrow in the circulation and whether this release can be
inhibited by bevacizumab. After these two cohorts we will proceed with the
second part B of the study with two different dosing schedules of Docetaxel and
Paclitaxel if indeed a release of progenitor cells upon treatment with either
Docetaxel or Paclitaxel occurred.
Intervention
Patients will be randomly assigned to cohorts, with or without a predose
consisting of bevacizumab.
Other interventions include venapunctures for bloodsampling.
Study burden and risks
Extent of burden for the participating patients consitst mainly of the time
that they have to spent extra in the hospital, and the times they have to come
back to the hospital. Also the extra bloodsampling by a second iv catheter
might be a burden.
The administration of bevacizumab can cause side effects which can also be a
burden.
The benefit for the patients is the addition of bevacizumab to the regular
treatment.
Heidelberglaan 100
3584 CX Utrecht
Nederland
Heidelberglaan 100
3584 CX Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
The patient will have a previous diagnosis of histologically or cytologically documented solid tumor.
The patient will start a taxane containing regimen as first or second line chemotherapy according to standard treatment guidelines for the underlying disease. Patients with metastatic or locally advanced breast cancer will be eligible.
The patient has given written informed consent.
The patient is willing and able to comply with protocol procedures.
The patient must be *18 years of age.
The patient will have not received any chemotherapy or biological therapy within the last 28 days and has recovered from any acute effects.
Performance status WHO 0-2
Exclusion criteria
Surgery < 3 weeks prior to the start of study treatment
Inadequate recovery from previous surgery, radiation, chemo-, biologic or immunotherapy
Patients who have known hypersensitivity to the study medication, ie bevacizumab and taxane containing chemotherapy
concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study (details in protocol)
Laboratory evaluation disturbances (details in protocol)
Previous neuropathy grade II
Squamous cell tumors adjacent to the large thoracic vasculature
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 | EUCTR2007-004119-79-NL |
| CCMO | NL18958.041.07 |