Antisecretory Factor in Primary Glioblastoma 1

Overview

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.

Full Title of Study: “Antisecretory Factor, Administered as an Enriched Egg Powder, Salovum®, as Supplementary Therapy for Primary Glioblastoma During Concomitant Radio-chemotherapy.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 31, 2021

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.

Interventions

  • Dietary Supplement: Salovum
    • Egg yolk powder enriched for anti secretory factor

Arms, Groups and Cohorts

  • Experimental: Salovum
    • Salovum®, an egg powder enriched for anti secretory factor.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. Pathology verified glioblastoma 2. Age 18-69 years 3. Surgical treatment-biopsy or resection. 4. Scheduled full concomitant radiochemotherapy treatment with radiation (60 Gy) and temozolomide, 5. Informed consent Exclusion Criteria:

1. No informed consent 2. Egg yolk allergy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 69 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Peter Siesjö
  • Collaborator
    • Region Skane
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Peter Siesjö, Professor – Skane University Hospital
  • Overall Official(s)
    • Peter Siesjö, MD, PhD, Principal Investigator, Skane University Hospital

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