Antisecretory Factor Glioblastoma Phase 2

Study Overview
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Brief Summary
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This is a randomised, double blinded and multiple center , Phase 2 study in patients with newly diagnosed glioblastoma. Participants will receive an egg powder enriched for antisecretory factor (AF), Salovum, or a placebo egg powder daily from 2 days before concomitant radio-chemo therapy or chemotherapy until 14 days after finalisation plus during adjuvant chemotherapy.The primary aims of are overall survival at 6 and 12 months after diagnosis

Detailed Description
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Glioblastoma (GB) 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 with antisecretory and anti-inflammatory effects. 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 an din other countries. 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. 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. Intratumoral delivery of AF-16 potentiated the effect of intratumoral temozolomide in an experimental model of glioblastoma. 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. In a completed phase1-2 trial in participants with primary gliobalstoma the add on of Salovum during concomitant radiochemotherapa was considered safe and feasible. The current study is aimed at assessing the efficacy of Salovum in a RCT (randomised controlled trail).

Official Title
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Antisecretory Factor During Concomitant and Adjuvant Therapy of Primary Glioblastoma, a Randomised, Prospective and Double Blinded Study

Conditions
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Glioblastoma

Intervention / Treatment
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* Dietary Supplement: Salovum
* Dietary Supplement: Placebo egg yolk powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathology verified glioblastoma or astrocytoma grade 4 Age 18-75 years Surgical treatment-resection. Scheduled concomitant radiochemotherapy, or only chemotherapy. Informed consent Exclusion Criteria: No informed consent Egg yolk allergy Only surgical biopsy Only radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, prospective, double blinded
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Salovum<br>Salovum, an egg yolk powder will be orally at dose of 11 g 3 times daily. | Dietary Supplement: Salovum<br>* Salovum is an eggyolkpowder derived from hens fed with SPC (specially processed cereals) and contains increased amounts of the endogenous protein antisecretory factor.<br>* Other names: Antisecretory factor;|
| Placebo Comparator: Placebo<br>Placebo, an egg yolk powder will be orally at dose of 11 g 3 times daily. | Dietary Supplement: Placebo egg yolk powder<br>* Egg yolk powder derived from hen fed with normal feed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Survival | up to 12 months from primary surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival at 6 and 12 months | Progress free survival as a compound assessment by a multidisciplinary conference (MDC) | At 6 and 12 months from primary surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antisecretory factor, Trials, Randomized Clinical