Antisecretory Factor in Primary Glioblastoma 1

Glioblastoma Clinical Trial

— AFGBM1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04116138
• Other study ID #: AFGBM1
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 1, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: November 2020
• Source: Skane University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Edema
• Cerebral Edema
• Chemotherapy Effect
• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
Sweden	Department of Neurosurgery	Lund

Sponsors (5)

Lead Sponsor	Collaborator
Peter Siesjö	Lantmannen Medical AB, Lund University, Region Skane, Skane University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive function	Number of participants with decreased cognitive function assessed by Mini Mental State Examination (MMSE)	Change from baseline at day 20, 57 and 70.
Other	Number of participants with decreased neurological function	Neurologic function assessed by Neurologic Assessment in Neuro-Oncology (NANO) scale. Minimum 0 (no deficits) and maximum 25 (maximum deficits)	Change from baseline at day 20, 57 and 70.
Other	Number of participants with decreased performance	Number of participants with decreased performance assessed by Eastern Oncology Cooperative Group (ECOG) scale. Minum 0 (normal function) and maximum 4 (maximum disability)	Change from baseline at day 20, 57 and 70.
Other	Number of participants with decreased quality of life	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	Change from baseline at day 20, 57 and 70.
Primary	Number of participants with treatment-related adverse	Treatment related adverse events as assessed by CTCAE v 5.0	Cumulative from day 1 to 80
Primary	Number of participants with completion of prescribed Salovum treatment	Defined as completing prescribed full Salovum treatment	Cumulative from day 1 to 80
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.