Role of Antisecretory Factor in Curative Radiochemotherapy for Anal Carcinoma

Anal Cancer Clinical Trial

— SALFLAC  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05351931
• Other study ID #: ASF 3
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2022
• Est. completion date: March 2024

Study information

• Verified date: April 2022
• Source: Uppsala University Hospital
• Contact: Peter Nygren, MD
• Phone: +46704250719
• Email: peter.nygren[@]igp.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 38
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms

Intervention

Dietary Supplement:
• Salovum and SPC-flakes or corresponding placebo
Salovum and SPC-flakes are foods approved for specific medical purposes.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Uppsala University Hospital	Lantmännen AB, Onkologiska klinikens forskningsfond, Sjöbergstiftelsen, Swedish Cancer Society

References & Publications (6)

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. Review. — View 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. — View Citation

Johansson E, Jennische E, Lange S, Lönnroth I. Antisecretory factor suppresses intestinal inflammation and hypersecretion. Gut. 1997 Nov;41(5):642-5. — View Citation

Laurenius A, Wängberg 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. — View Citation

Lönnroth 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of AEs CTCAEv5.0 grade = 2 considered probably related to investigational products/placebo.	Adverse effects from study products	Through study completion, approximately 6 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	Relationships between P-ASF concentration, biomarkers reflecting inflammation and adverse events.	Biomarker assessments	Through study completion, approximately 6 months
Secondary	Differences in primary and secondary endpoints between Salovum and placebo subgroups.	Assessment of added value of Salovum	Through study completion, approximately 6 months
Secondary	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
Secondary	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