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van CCT (UK)

van CCT (UK)

Angiogenic factor expression during fractionated irradiation

- candidate number16501
- NTR NumberNTR4440
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR18-feb-2014
- Secondary IDs2013/340 METC VU
- Public TitleAngiogenic factor expression during fractionated irradiation
- Scientific TitlePilot study to determine the effect of fractionated radiotherapy on expression of pro-angiogenic factors in oeshophagus carcinoma
- hypothesisThis study has 2 primary objectives: 1) To determine the time point of induction of VEGF expression in the tumour tissue of oesophagus carcinomas during chemoradiation. 2) To determine whether the tumour promoting effects of this induction of VEGF expression can be inhibited by administration of bevacizumab.
- Healt Condition(s) or Problem(s) studiedEsophageal cancer, Neoadjuvant chemoradiatian
- Inclusion criteria(1) Histological confirmation of adenocarcinoma/squamous cell carcinoma of the oesophagus (2) Patients that will receive standard chemoradiation treatment before surgery for oesophageal carcinoma (3) Ability to give informed consent (4) Age 18 years or older (5) no prior therapy for oesophageal carcinoma
- Exclusion criteria(1) pregnancy (2) Inflammation of the gastro-intestinal tract (3) Brain metastasis (4) Diastolic/ systolic Hypertension (>90/>140 mmHg), not responding to treatment (5) Arterial thromboembolism in medical history (6) Surgery within the month prior to start of bevacizumab treatment
- mec approval receivedyes
- multicenter trialno
- randomisedno
- groupParallel
- TypeSingle arm
- Studytypeintervention
- planned startdate 20-feb-2014
- planned closingdate20-feb-2016
- Target number of participants40
- InterventionsPatients will undergo 1 extra endoscopic biopsy to collect tumour tissue. In addition, on four time points blood samples will be collected. The time point of this biopsy and blood collection depends on the study cohort. The patients in the final cohort will receive bevacizumab (3mg/kg/wk) starting at the identified time point of induction. Bevacizumab administration will be discontinued 4 weeks before the surgical resection of the tumour.
- Primary outcomeThe primary parameter is the alteration of the VEGF expression on mRNA level in the tumour before and during the course of neoadjuvant chemoradiation. In addition, in the bevacizumab treated cohort, the primary parameter is the activity (phosphorylation) of the VEGF receptor (VEGFR) in the tumour tissue obtained with biopsy and the microvessel density of the resection material of the tumour
- Secondary outcome(1) Determination of mRNA expression levels of other pro-angiogenic factors than VEGF and factors that may influence radiosensitivity in the tumour tissue. (2) Determination of protein expression of pro-angiogenic factors and factors that may influence radiosensitivity in the tumour tissue with IHC. (3) Determination of Epstein Barr virus (EBV) status in the tumour tissue. (4) Quantification of vascular parameters in the tumour tissue to assess on-going angiogenesis. (5) Measurement of the plasma concentration of pro-angiogenic factors to determine if this correlates with the expression levels in the tumour tissue. (6) Determination of the expression level of angioregulatory miRNAs in the tumour tissue to assess whether this is affected during neoadjuvant chemoradiation.
- TimepointsBefore chemoradiation during chemoradiation after chemoradiation surgery
- Trial web site
- statusopen: patient inclusion
- Sponsor/Initiator VU University Medical Center
- Funding
(Source(s) of Monetary or Material Support)
VU University Medical Center
- Publications
- Brief summaryEvidence is emerging that the effect of radiotherapy might be enhanced by angiostatic drugs. Whereas preclinical results are promising, clinical trials have shown only moderate effect so far. This is most likely due to suboptimal scheduling; both modalities have to be precisely dosed and scheduled to gain the optimal effect, with the lowest possible toxicity. Our results show that fractionated irradiation in vitro and in vivo induces a fast and significant up-regulation of pro-angiogenic factors. These results indicate that the long term anti-tumour effects of radiotherapy might be enhanced by inhibiting the pro-angiogenic response induced during the course of radiotherapy. Whether and when this pro-angiogenic response to radiotherapy occurs in patients remains elusive. Therefore, it is important to determine the time point at which the proangiogenic response during fractionated radiotherapy develops in patients. Furthermore, it is important to determine whether this up-regulation can be inhibited by the administration of bevacizumab, a monoclonal antibody against VEGF. In this way an optimal dose schedule could be designed for the combination treatment of angiostatic drugs and radiotherapy.
- Main changes (audit trail)
- RECORD18-feb-2014 - 7-apr-2014

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