Antisecretory Factor in Primary Glioblastoma 1

Study Overview
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Brief Summary
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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
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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.

Official Title
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Antisecretory Factor, Administered as an Enriched Egg Powder, Salovum®, as Supplementary Therapy for Primary Glioblastoma During Concomitant Radio-chemotherapy.

Conditions
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Glioblastoma, Cerebral Edema, Chemotherapy Effect

Intervention / Treatment
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* Dietary Supplement: Salovum


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1-2, open label, single arm, single center.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salovum<br>Salovum®, an egg powder enriched for anti secretory factor. | Dietary Supplement: Salovum<br>* Egg yolk powder enriched for anti secretory factor<br>* Other names: Antisecretory factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse | Treatment related adverse events as assessed by CTCAE v 5.0 | Cumulative from day 1 to 80 | 
| Number of participants with completion of prescribed Salovum treatment | Defined as completing prescribed full Salovum treatment | Cumulative from day 1 to 80 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with altered blood levels of triglycerides and cholesterol | Blood levels of triglyceride and cholesterol above normal range or increased from baseline | Change from baseline at day 20, 57 and 70. | 
| Number of participants with reduced or no steroid intake | Intake of oral corticosteroids assessed weekly during and after intervention. | Change from baseline at day 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70. | 
| Number of participants with detetable blood levels antisecretory factor | Analysis of anti secretory factor-16 (AF-16) blood levels by enzyme linked immunoassay | Change from baseline at day 20, 57 and 70. | 
| 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 | Change from baseline at day 20, 57 and 70. |