Antisecretory Factor in Primary Glioblastoma 1 (AFGBM1)
Primary Purpose
Glioblastoma, Cerebral Edema, Chemotherapy Effect
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Salovum
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Pathology verified glioblastoma
- Age 18-69 years
- Surgical treatment-biopsy or resection.
- Scheduled full concomitant radiochemotherapy treatment with radiation (60 Gy) and temozolomide,
- Informed consent
Exclusion Criteria:
- No informed consent
- Egg yolk allergy
Sites / Locations
- Department of Neurosurgery
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Salovum
Arm Description
Salovum®, an egg powder enriched for anti secretory factor.
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse
Treatment related adverse events as assessed by CTCAE v 5.0
Number of participants with completion of prescribed Salovum treatment
Defined as completing prescribed full Salovum treatment
Secondary Outcome Measures
Number of participants with altered blood levels of triglycerides and cholesterol
Blood levels of triglyceride and cholesterol above normal range or increased from baseline
Number of participants with reduced or no steroid intake
Intake of oral corticosteroids assessed weekly during and after intervention.
Number of participants with detetable blood levels antisecretory factor
Analysis of anti secretory factor-16 (AF-16) blood levels by enzyme linked immunoassay
Number of participants with altered blood levels of inflammatory cytokines
Analysis of interleukin-6 (IL-6), interleukin- (IL-8), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a), macrophage inflammatory protein-1b (MIP-1b) by multiplex analysis
Full Information
NCT ID
NCT04116138
First Posted
September 26, 2019
Last Updated
April 27, 2021
Sponsor
Peter Siesjö
Collaborators
Region Skane, Lund University, Skane University Hospital, Lantmannen Medical AB
1. Study Identification
Unique Protocol Identification Number
NCT04116138
Brief Title
Antisecretory Factor in Primary Glioblastoma 1
Acronym
AFGBM1
Official Title
Antisecretory Factor, Administered as an Enriched Egg Powder, Salovum®, as Supplementary Therapy for Primary Glioblastoma During Concomitant Radio-chemotherapy.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
March 31, 2021 (Actual)
Study Completion Date
March 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Peter Siesjö
Collaborators
Region Skane, Lund University, Skane University Hospital, Lantmannen Medical AB
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a non-randomised, open-label, single center-centre, Phase I-II study in patients with newly diagnosed glioblastoma. 5 patients with newly diagnosed glioblastoma are enrolled in the study and will receive an egg powder enriched for antisecretory factor (AF), Salovum, daily from 2 days before concomitant radio-chemo therapy until 14 days after finalisation.The primary aim of the study is to asses safety and feasibility of this regimen.
Detailed Description
Glioblastoma (GBM) is the most common primary brain tumor and also has the worst prognosis with a mean survival time below 1 year and a 5-year survival rate of less than 2%.
AF is a 41kilodalton endogenous and essential protein encompassing antisecretory and anti-inflammatory effect. Endogenous AF activity increases after exposure to bacterial toxins and endogenous triggers of inflammation. The active amino-terminal portion of AF has been synthesized as a 16 amino acid peptide (AF-16) and has been used in animal experimental studies. Salovum® is a product based on egg yolk powder B221® and contains high levels of AF. Salovum® is classified as food for special medicinal purposes (FSMP) by the European Union.
Many tumors show elevated interstitial fluid pressure (IFP) compared to the surrounding tissue due to vascular leakage, providing a barrier for drug uptake in solid tumors, as well as poor perfusion, resulting in hypoxia and relative resistance to radiochemotherapy.
In a mouse model of malignant brain tumor, preliminary findings show that intratumoral infusion of AF-16 greatly enhances the effect of simultaneous intratumoral temozolomide treatment (90% and 40% survival, respectively). AF-16 also has preliminarily significant immune modulatory effects on myeloid cells in vitro, but also effects on the secretion of immune modulatory agents from tumor cells. AF-16 was reported to significantly reduce the IFP in xenotransplanted human glioblastoma by inhibiting an ionic pump, NKCC1, in the tumor tissue. Both Salovum® and AF-inducing specific processed cereals (SPC) prolonged survival in the same models. Systemic temozolomide treatment combined with AF inducing SPC completely blocked tumor growth in GBM xenografts. Likewise, SPC treatment abrogated 90% of pre-established syngeneic tumors in immune competent animals.
Mechanistically, it remains unclear whether AF's effect in tumor models is mediated through decrease of IFP and/or immunomodulation. Also, an effect on the complement system through modulation of circulating complement complexes with proteasome units has been proposed.
Salovum® has been administered to patients with various diseases as, inflammatory bowel disease, Mb Ménière and mastitis and traumatic brain injury without signs of any adverse effects.
The described study is a safety and feasibility study and if these criteria are fulfilled, will be followed by a randomised controlled trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Cerebral Edema, Chemotherapy Effect
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 1-2, open label, single arm, single center.
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Salovum
Arm Type
Experimental
Arm Description
Salovum®, an egg powder enriched for anti secretory factor.
Intervention Type
Dietary Supplement
Intervention Name(s)
Salovum
Other Intervention Name(s)
Antisecretory factor
Intervention Description
Egg yolk powder enriched for anti secretory factor
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse
Description
Treatment related adverse events as assessed by CTCAE v 5.0
Time Frame
Cumulative from day 1 to 80
Title
Number of participants with completion of prescribed Salovum treatment
Description
Defined as completing prescribed full Salovum treatment
Time Frame
Cumulative from day 1 to 80
Secondary Outcome Measure Information:
Title
Number of participants with altered blood levels of triglycerides and cholesterol
Description
Blood levels of triglyceride and cholesterol above normal range or increased from baseline
Time Frame
Change from baseline at day 20, 57 and 70.
Title
Number of participants with reduced or no steroid intake
Description
Intake of oral corticosteroids assessed weekly during and after intervention.
Time Frame
Change from baseline at day 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70.
Title
Number of participants with detetable blood levels antisecretory factor
Description
Analysis of anti secretory factor-16 (AF-16) blood levels by enzyme linked immunoassay
Time Frame
Change from baseline at day 20, 57 and 70.
Title
Number of participants with altered blood levels of inflammatory cytokines
Description
Analysis of interleukin-6 (IL-6), interleukin- (IL-8), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a), macrophage inflammatory protein-1b (MIP-1b) by multiplex analysis
Time Frame
Change from baseline at day 20, 57 and 70.
Other Pre-specified Outcome Measures:
Title
Cognitive function
Description
Number of participants with decreased cognitive function assessed by Mini Mental State Examination (MMSE)
Time Frame
Change from baseline at day 20, 57 and 70.
Title
Number of participants with decreased neurological function
Description
Neurologic function assessed by Neurologic Assessment in Neuro-Oncology (NANO) scale. Minimum 0 (no deficits) and maximum 25 (maximum deficits)
Time Frame
Change from baseline at day 20, 57 and 70.
Title
Number of participants with decreased performance
Description
Number of participants with decreased performance assessed by Eastern Oncology Cooperative Group (ECOG) scale. Minum 0 (normal function) and maximum 4 (maximum disability)
Time Frame
Change from baseline at day 20, 57 and 70.
Title
Number of participants with decreased quality of life
Description
Number of participants with decreased quality of life assessed by European Organization of Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30 and brain cancer module (BN20) questionnaire
Time Frame
Change from baseline at day 20, 57 and 70.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathology verified glioblastoma
Age 18-69 years
Surgical treatment-biopsy or resection.
Scheduled full concomitant radiochemotherapy treatment with radiation (60 Gy) and temozolomide,
Informed consent
Exclusion Criteria:
No informed consent
Egg yolk allergy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Siesjö, MD, PhD
Organizational Affiliation
Skane University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurosurgery
City
Lund
ZIP/Postal Code
22185
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
As there are only 5 patients in this study individual patient data without age and gender will be shared after publication
IPD Sharing Time Frame
De identified individual patient data will be made available from 3 months after publication up to 24 months after publication
IPD Sharing Access Criteria
By request from researcher
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Antisecretory Factor in Primary Glioblastoma 1
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