Clinical trial NCT05669820: Antisecretory Factor Glioblastoma Phase 2
Official title: Antisecretory Factor During Concomitant and Adjuvant Therapy of Primary Glioblastoma, a Randomised, Prospective and Double Blinded Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Glioblastoma
Keywords: Antisecretory factor
Trials, Randomized Clinical
Lead sponsor: Skane University Hospital
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2023-01-03
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, prospective, double blinded
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Pathology verified glioblastoma or astrocytoma grade 4
2. Age 18-75 years
3. Surgical treatment-resection.
4. Scheduled concomitant radiochemotherapy, or only chemotherapy.
5. Informed consent

Exclusion Criteria:

1. No informed consent
2. Egg yolk allergy
3. Only surgical biopsy
4. Only radiotherapy

Primary outcomes:
measure: Overall survival
timeFrame: up to 12 months from primary surgery
Secondary outcomes:
measure: Progress free survival at 6 and 12 months
timeFrame: At 6 and 12 months from primary surgery
Other outcomes:
measure: Cognitive function
timeFrame: up to 1 year
measure: Neurological function
timeFrame: up to 1 year
measure: QOL Assessed by European Organization of Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30
timeFrame: up to 1 years
measure: quality of life (QOL) assessed by brain cancer module (BN20) questionnaire
timeFrame: up to 1 years
measure: Performance Assessed by Eastern Oncology Cooperative Group (ECOG) performance scale
timeFrame: up to 1 year
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital
Study officials:
affiliation: Skane University Hospital
name: Charlotte Edwardsson
role: STUDY_CHAIR
affiliation: Skane University Hospital
name: Erik Ehinger, MD
role: STUDY_CHAIR
References: