Angiogenic Factor Expression During Fractionated Irradiation

Early Phase 1

• Conditions: Primary Esophageal Carcinoma
• Interventions: Drug: Bevacizumab

• Registration Number: NCT02072720
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

The main question of this study is if and when VEGF (vascular endothelial growth factor) expression in the tumor is upregulated during chemoradiation and if bevacizumab inhibits subsequent vessel growth in the tumor.

* Therefore the first aim of this study is to identify the time point of induction of VEGF in the tumor tissue of esophagus carcinoma during chemoradiation (after 1,2,3 or 4 weeks of chemoradiation).

* If we identify increased expression of VEGF at a certain time point, our second aim is to determine if we can inhibit the subsequent tumor vessel growth by administration of bevacizumab.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-19
• Study First Submitted QC: 2014-02-24
• Study First Posted: 2014-02-26
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-01
• Last Update Posted: 2019-10-02
• Primary Completion: 2021-03
• Study Completion: 2021-05-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• patients that will receive chemoradiation following CROSS-schedule before surgery for esophageal carcinoma
• ability to give informed consent
• age 18 years or older

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Exclusion Criteria

• pregnancy
• evidence of bleeding diathesis, coagulopathy
• inflammation of the GI-tract
• brain metastases
• diastolic/ systolic hypertension, not responding to treatment
• arterial thromboembolism in medical history
• surgery within the month prior to start of bevacizumab treatment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
bevacizumab	Bevacizumab	These patients will receive bevacizumab once a week during their chemoradiation, starting at the identified time point of enhanced VEGF expression. These patients will also undergo and pre-treatment tumor biopsy and 1 tumor biopsy 1 week after the start of bevacizumab treatment.

Primary Outcome Measures

Name	Time	Method
Change of VEGF mRNA expression in tumor biopsies	5 weeks	To compare the VEGF mRNA expression in the pre-treatment and on-treatment tumor biopsies, to measure the change in VEGF expression from baseline.
Change of VEGFR2 phosphorylation with IHC	8 weeks	To determine the level of pVEGFR2 expression in tumor biopsies of patients that received bevacizumab, and to compare that to their pre-treatment expression levels, to identify the changes in expression from baseline.

Secondary Outcome Measures

Name	Time	Method
Changes of mRNA expression of other pro-angiogenic factors	5 weeks	To identify the expression of other pro-angiogenic factors in the tumor, and to measure the changes from baseline expression (pre-treatment vs on-treatment biopsies).
Changes in protein expression of pro-angiogenic factors	5 weeks	To identify the protein expression of other pro-angiogenic factors in the tumor, and to measure the changes from baseline expression (pre-treatment vs on-treatment biopsies).
Changes in vascular parameters in the tumor tissue to asses ongoing angiogenesis	5 weeks	To identify the expression of CD31+ and pericyte markers with IHC staining in the tumor, and to measure the changes from baseline expression (pre-treatment vs on-treatment biopsies).

Trial Locations

Locations (3)

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

VU university medical center; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Academisch Medisch Centrum; 🇳🇱 Amsterdam, Netherlands