Antisecretory Factor in Primary Glioblastoma 1 (AFGBM1)

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Chemotherapy Effect; Cerebral Edema
• Intervention / Treatment: Dietary supplement: Salovum

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22185
    • Department of Neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Salovum; Salovum®, an egg powder enriched for anti secretory factor.	Dietary supplement: Salovum; Egg yolk powder enriched for anti secretory factor; Other Names: Antisecretory factor

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Peter Siesjö
• Collaborators: Lund University; Region Skane; Skane University Hospital; Lantmannen Medical AB
• Investigators: Principal Investigator: Peter Siesjö, MD, PhD, Skane University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Brain Edema; Gastrointestinal Agents; Antidiarrheals; Antisecretory factor
• Other Study ID Numbers: AFGBM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No