Clinical trial NCT05351931: Role of Antisecretory Factor in Curative Radiochemotherapy for Anal Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anal Cancer
Keywords: Radiochemotherapy
Adverse event
Antisecretory factor
Lead sponsor: Uppsala University Hospital
Sponsor class: OTHER
Collaborators: name: Lantmännen AB
name: Sjöbergstiftelsen
name: Onkologiska klinikens forskningsfond
name: Swedish Cancer Society
First posted: 2022-04-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized parallel two groups
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Through study completion, approximately 6 months
Secondary outcomes:
measure: Incidence and severity of other AEs according to CTCAEv5.0 during and up to 6 months after RCT.
timeFrame: Through study completion, approximately 6 months
measure: 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.
timeFrame: Through study completion, approximately 6 months
measure: Increase in plasma (P)-ASF concentration from baseline to the day of start of RCT and to the end of treatment.
timeFrame: Days -1, 6 and 42
measure: Relationships between P-ASF concentration, biomarkers reflecting inflammation and adverse events.
timeFrame: Through study completion, approximately 6 months
measure: Differences in primary and secondary endpoints between Salovum and placebo subgroups.
timeFrame: Through study completion, approximately 6 months
measure: Tumour response rate according to RECIST v1.1 and clinical examination at 2, 3 (radiology) and 6 months after stop of RCT.
timeFrame: Through study completion, approximately 6 months
measure: Disease free and overall survival at 3 and 6 months after stop of RCT.
timeFrame: At 3 and 6 months after stop of treatment
Other outcomes:
measure: Incidence of AEs CTCAEv5.0 grade ≥ 2 considered probably related to investigational products/placebo.
timeFrame: Through study completion, approximately 6 months
Locations:
Study officials:
References:
citation: Cinausero M, Aprile G, Ermacora P, Basile D, Vitale MG, Fanotto V, Parisi G, Calvetti L, Sonis ST. New Frontiers in the Pathobiology and Treatment of Cancer Regimen-Related Mucosal Injury. Front Pharmacol. 2017 Jun 8;8:354. doi: 10.3389/fphar.2017.00354. eCollection 2017.
citation: Ulgheri C, Paganini B, Rossi F. Antisecretory factor as a potential health-promoting molecule in man and animals. Nutr Res Rev. 2010 Dec;23(2):300-13. doi: 10.1017/S0954422410000193. Epub 2010 Aug 5.
citation: Johansson E, Jennische E, Lange S, Lonnroth I. Antisecretory factor suppresses intestinal inflammation and hypersecretion. Gut. 1997 Nov;41(5):642-5. doi: 10.1136/gut.41.5.642.
citation: Lonnroth I, Lange S. Purification and characterization of the antisecretory factor: a protein in the central nervous system and in the gut which inhibits intestinal hypersecretion induced by cholera toxin. Biochim Biophys Acta. 1986 Aug 6;883(1):138-44. doi: 10.1016/0304-4165(86)90144-3.
citation: Laurenius A, Wangberg B, Lange S, Jennische E, Lundgren BK, Bosaeus I. Antisecretory factor counteracts secretory diarrhoea of endocrine origin. Clin Nutr. 2003 Dec;22(6):549-52. doi: 10.1016/s0261-5614(03)00057-8.
citation: Eriksson A, Shafazand M, Jennische E, Lange S. Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial. Scand J Gastroenterol. 2003 Oct;38(10):1045-9. doi: 10.1080/00365520310005064.