Angiogenic Factor Expression During Fractionated Irradiation

October 1, 2019 updated by: H.M.W. Verheul, Amsterdam UMC, location VUmc

Pilot Study to Determine the Effect of Fractionated Radiotherapy on Expression of Pro-angiogenic Factors in Oesophagus Carcinoma

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
      • Alkmaar, Netherlands
        • Recruiting
        • Noordwest Ziekenhuisgroep
        • Contact:
          • A. M. Van Berkel
      • Amsterdam, Netherlands
        • Recruiting
        • Academisch Medisch Centrum
        • Contact:
          • H. W.M. van Laarhoven
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1081 HV
        • Recruiting
        • VU University Medical Center
        • Principal Investigator:
          • Henk Verheul, MD/PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: on-treatment tumor biopsie
patients will undergo an pre-treatment and on-treatment tumor biopsy, to measure VEGF expression, and identify the time point of induction of VEGF expression.
Experimental: 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.
Drug: Bevacizumab
patients will receive bevacizumab (3mg/kg/wk) starting from the identified induction time point of VEGF expression
Other Names:
  • Bevacizumab (Avastin).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of VEGF mRNA expression in tumor biopsies
Time Frame: 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.
5 weeks
Change of VEGFR2 phosphorylation with IHC
Time Frame: 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.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of mRNA expression of other pro-angiogenic factors
Time Frame: 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).
5 weeks
Changes in protein expression of pro-angiogenic factors
Time Frame: 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).
5 weeks
Changes in vascular parameters in the tumor tissue to asses ongoing angiogenesis
Time Frame: 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).
5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Noordwest Ziekenhuisgroep

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Anticipated)

March 1, 2021

Study Completion (Anticipated)

May 1, 2021

Study Registration Dates

First Submitted

February 19, 2014

First Submitted That Met QC Criteria

February 24, 2014

First Posted (Estimate)

February 26, 2014

Study Record Updates

Last Update Posted (Actual)

October 2, 2019

Last Update Submitted That Met QC Criteria

October 1, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013/340

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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