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Angiogenic Factor Expression During Fractionated Irradiation

Primary Purpose

Primary Esophageal Carcinoma

Status
Unknown status
Phase
Early Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Bevacizumab
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Esophageal Carcinoma focused on measuring Radiotherapy, VEGF, esophagus carcinoma, bevacizumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VU university medical centerRecruiting
  • Noordwest ZiekenhuisgroepRecruiting
  • Academisch Medisch CentrumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

on-treatment tumor biopsie

bevacizumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change of VEGF mRNA expression in tumor biopsies
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
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

Changes of mRNA expression of other pro-angiogenic factors
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
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
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).

Full Information

First Posted
February 19, 2014
Last Updated
October 1, 2019
Sponsor
Amsterdam UMC, location VUmc
Collaborators
Noordwest Ziekenhuisgroep, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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1. Study Identification

Unique Protocol Identification Number
NCT02072720
Brief Title
Angiogenic Factor Expression During Fractionated Irradiation
Official Title
Pilot Study to Determine the Effect of Fractionated Radiotherapy on Expression of Pro-angiogenic Factors in Oesophagus Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 2014 (undefined)
Primary Completion Date
March 2021 (Anticipated)
Study Completion Date
May 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
Noordwest Ziekenhuisgroep, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Esophageal Carcinoma
Keywords
Radiotherapy, VEGF, esophagus carcinoma, bevacizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
on-treatment tumor biopsie
Arm Type
No Intervention
Arm Description
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.
Arm Title
bevacizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Bevacizumab (Avastin).
Intervention Description
patients will receive bevacizumab (3mg/kg/wk) starting from the identified induction time point of VEGF expression
Primary Outcome Measure Information:
Title
Change of VEGF mRNA expression in tumor biopsies
Description
To compare the VEGF mRNA expression in the pre-treatment and on-treatment tumor biopsies, to measure the change in VEGF expression from baseline.
Time Frame
5 weeks
Title
Change of VEGFR2 phosphorylation with IHC
Description
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.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Changes of mRNA expression of other pro-angiogenic factors
Description
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).
Time Frame
5 weeks
Title
Changes in protein expression of pro-angiogenic factors
Description
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).
Time Frame
5 weeks
Title
Changes in vascular parameters in the tumor tissue to asses ongoing angiogenesis
Description
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).
Time Frame
5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henk Verheul, MD/ PhD
Email
h.verheul@vumc.nl
Facility Information:
Facility Name
VU university medical center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henk Verheul, MD/PhD
Facility Name
Noordwest Ziekenhuisgroep
City
Alkmaar
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A. M. Van Berkel
Facility Name
Academisch Medisch Centrum
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H. W.M. van Laarhoven

12. IPD Sharing Statement

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Angiogenic Factor Expression During Fractionated Irradiation

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