Role of Antisecretory Factor in Curative Radiochemotherapy for Anal Carcinoma

Study Overview
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Brief Summary
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Curative radiochemotherapy (RCT) for anal carcinoma (AC) is associated with considerable acute and long-term toxicity. The acute toxicity derives from the combined effects of radiation and chemotherapy and is dominated by localized skin mucositis, diarrhoea and pain from radiation and nausea, fatigue, anemia/leukopenia, diarrhoea and general skin dryness from chemotherapy. Cholera induced diarrhoea, as well as other forms of diarrhoea-inducing agents, has been shown to elicit a stimulated, endogenous production of a protein, named antisecretory factor (ASF). This protein has been chemically characterized in detail. ASF acts by modulating secretion of water and ions but also counteracts inflammatory processes. With this background the present study will investigate if induction of endogenous ASF by intake of SPC-flakes might be beneficial in AC patients to prevent RCT induced adverse events (AEs) and if administration of ASF from Salovum provides additional benefit (explorative).

Detailed Description
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Curative RCT for AC is associated with considerable acute and long-term toxicity. The acute toxicity derives from the combined effects of radiation and chemotherapy and is dominated by localized skin mucositis, diarrhoea and pain from radiation and nausea, fatigue, anemia/leukopenia, diarrhoea and general skin dryness from chemotherapy. These adverse effects are treated symptomatically with mostly modest effect and sometimes leads to the need for in-patient care and temporary stop of the RCT. Long-term toxicity is caused by radiation fibrosis and is dominated by impaired anal sphincter function leading to faeces incontinence, pelvic pain and reduced sexual function. Thus, new ways to efficiently counteract the RCT induced adverse effects are urgently needed. Cholera induced diarrhoea, as well as other forms of diarrhoea-inducing agents, has been shown to elicit a stimulated, endogenous production of a protein, named antisecretory factor (ASF). This protein has been chemically characterized in detail. ASF acts by modulating secretion of water and ions but also counteracts inflammatory processes . ASF is also produced by hens fed on a diet of fermented grains or a specific diet of sugars and amino acids, leading to an accumulation of the ASF protein in the egg yolk. Spray dried yolk in the form of a powder is commercialized as Salovum registered by the EU authorities as Food for specific medical purposes, i e is not adrug from a regulatory perspective. Salovum rapidly increase the plasma (P-) ASF-concentration. Another way to increase ASF and, thus, to achieve benefit, is to induce its production/conversion by ingestion of oat flakes, specially processed (similar to malting) to contain the proper mix of sugars and amino acids. Such flakes are also commercially available (named SPC flakes) as Food for specific medical purposes and has been recommended or considered for a number of secretory pathological conditions, e g for treatment of Mb Meniére. With this background the present study will investigate if induction of endogenous ASF by intake of SPC-flakes might be beneficial in AC patients to prevent RCT induced adverse events (AEs) and if administration of ASF from Salovum provides additional benefit (explorative).

Official Title
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A Randomized Phase 2 Double-blind Placebo-controlled Trial Investigating the Effect of Salovum™ and SPC-flakes on Radiochemotherapy Induced Toxicity in Curative Treatment of Anal Carcinoma

Conditions
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Anal Cancer

Intervention / Treatment
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* Dietary Supplement: Salovum and SPC-flakes or corresponding placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Histologically confirmed diagnosis of AC irrespective of tumour p16-status. Planned for curative RCT according to national care programme schedule B WHO performance status of 0 or 1. For patients planned for schedule C, they must be unsuitable for or not consenting to participation in the SWANCA trial. Able to understand study information and questionnaires and provide signed informed consent. Exclusion Criteria: Patients with stoma. Contraindications to the investigational product, e g known or suspected hypersensitivity to the investigational products or expected inability to their use in accordance with the protocol. Contraindications to curative RCT in accordance with AC national care programme. Lack of suitability for participation in the study, e g expected difficulties to follow the protocol procedures, as judged by the investigator. Prior exposure to Salovum or SPC-flakes.

Ages Eligible for Study
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Minimum Age: 18 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 parallel two groups
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPC-flakes with or without Salovum<br>SPC-flakes flat dose of 75 g/d divided in 2 - 4 doses started 5 days prior to start of RCT and continued during the RCT. Salovum egg powder 4 g/sachet. Four sachets, ie 16 g q 8 h for 5 days prior to start of RCT. The appropriate amount of Salovum is mixed with 100 - 200 ml of suitable liquid, eg fruit juice, and ingested orally. | Dietary Supplement: Salovum and SPC-flakes or corresponding placebo<br>* Salovum and SPC-flakes are foods approved for specific medical purposes.<br>|
| Placebo Comparator: SPC-flakes placebo with or without Salovum placebo<br>SPC-placebo flat dose of 75 g/d divided in 2 - 4 doses started 5 days prior to start of RCT and continued during the RCT. Salovum placebo egg powder 4 g/sachet. Four sachets, ie 16 g q 8 h for 5 days prior to start of RCT. The appropriate amount of Salovum placebo is mixed with 100 - 200 ml of suitable liquid, eg fruit juice, and ingested orally. | Dietary Supplement: Salovum and SPC-flakes or corresponding placebo<br>* Salovum and SPC-flakes are foods approved for specific medical purposes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of diarrhoea, fecal urgency, anal skin toxicity/mucositis and anal pain CTCAEv5.0 ≥ grade 2 during and up to 6 months after RCT. Anal skin toxicity/mucositis is to be verified by photos. | Treatment related toxicity | Through study completion, approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of other AEs according to CTCAEv5.0 during and up to 6 months after RCT. | Other treatment related toxicity | Through study completion, approximately 6 months | 
| Change from baseline in patient reported hQoL and abdominal symptoms assessed by EORTC QLQ- 30 and the ANL27 subscale questionnaires as well as the Bristol Stool Form Scale. | PROMS | Through study completion, approximately 6 months | 
| Increase in plasma (P)-ASF concentration from baseline to the day of start of RCT and to the end of treatment. | Pharmacodynamic outcome and compliance check | Days -1, 6 and 42 | 
| Relationships between P-ASF concentration, biomarkers reflecting inflammation and adverse events. | Biomarker assessments | Through study completion, approximately 6 months | 
| Differences in primary and secondary endpoints between Salovum and placebo subgroups. | Assessment of added value of Salovum | Through study completion, approximately 6 months | 
| Tumour response rate according to RECIST v1.1 and clinical examination at 2, 3 (radiology) and 6 months after stop of RCT. | Assessment of benefit, if any, from study products on clinical outcome | Through study completion, approximately 6 months | 
| Disease free and overall survival at 3 and 6 months after stop of RCT. | Assessment of benefit, if any, from study products on clinical outcome | At 3 and 6 months after stop of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiochemotherapy, Adverse event, Antisecretory factor