Role of Antisecretory Factor in Curative Radiochemotherapy for Anal Carcinoma

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

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).

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).

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histologically confirmed diagnosis of AC irrespective of tumour p16-status.
3. Planned for curative RCT according to national care programme schedule B
4. WHO performance status of 0 or 1.
5. For patients planned for schedule C, they must be unsuitable for or not consenting to participation in the SWANCA trial.
6. Able to understand study information and questionnaires and provide signed informed consent.

Exclusion Criteria:

1. Patients with stoma.
2. 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.
3. Contraindications to curative RCT in accordance with AC national care programme.
4. Lack of suitability for participation in the study, e g expected difficulties to follow the protocol procedures, as judged by the investigator.
5. Prior exposure to Salovum or SPC-flakes.