Role of Antisecretory Factor in Dihydropyrimidine Treatment of Colorectal Cancer

NCT05339230 | Unknown

• 1 other identifier: ASF 2
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

One debilitating, and sometimes even life-threatening, toxicity from dihydropyrimidines, e g 5-FU and capecitabine, is gastrointestinal mucositis resulting in, eg severe diarrhoea necessitating in-hospital care including periods of support with iv fluids. The efficacy of current treatment for this adverse effect include iv fluids, loperamide and opioids po and octreotide sc is moderate and new treatment principles or, preferably, ways to prevent such toxicity, 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. 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". 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 (SPC-flakes) as "Food for specific medical purposes". Salovum has been shown to rapidly, ie within hours to a few days, antagonize diarrhoeal diseases of various etiologies. It has also been used against high fluid passages and inflammation in Crohns disease, Colitis ulcerosa and carcinoids in adults. SPC-flakes have similar effects but need weeks of administration to emerge. Interestingly from an oncological perspective, provision of exogenous ASF and induction of endogenous ASF has been shown to reduce interstitial fluid pressure (IFP) in tumours, increase tumour uptake of cytotoxic drugs and improve survival in animal tumour models. With this background the present study will investigate if administration of ASF in the form of Salovum combined with induction of endogenous ASF by intake of SPC-flakes might be beneficial in colorectal cancer (CRC) patients to prevent dihydropyrimidine based chemotherapy induced gastrointestinal mucositis and to reduce tumor interstitial fluid pressure .

Conditions

Dihydropyrimidine Induced Gastrointestinal Toxicity in Colorectal Cancer

Keywords

Dihydropyrimidine; Diarrhoea; Colorectal cancer; Antisecretory factor

Outcome Measures

Primary Outcomes (1)

• Incidence of diarrhoea CTCAEv5.0 ≥ grade 2.

  Chemotherapy induced toxicity to be counteracted by intervention

  During first 2 months of chemotherapy

Secondary Outcomes (7)

• Incidence of in-patient care for chemotherapy induced gastrointestinal mucositis including number of days in hospital and with parenteral fluids.

  During first 2 months of chemotherapy

• Change from baseline in patient reported hQoL and abdominal symptoms assessed by EORTC QLQ-30 and the colorectal cancer specific Q29 subscale.

  During first 2 months of chemotherapy

• Incidence and severity of other chemotherapy induced adverse effects according to CTCAEv5.0.

  During first 2 months of chemotherapy

• Increase in P-ASF concentration from baseline to day 7 from start of investigational product/placebo and just prior to treatment cycle 2, 3 and 4 (as applicable).

  During first 2 months of chemotherapy

• Relationships between P-ASF concentration and adverse effects.

  During first 2 months of chemotherapy

Other Outcomes (2)

• Change in liver metastasis water perfusion.

  One week prior to start of chemotherapy

• Change in liver metastasis tumor blood flow.

  One week prior to start of chemotherapy

Study Arms (2)

Active

EXPERIMENTAL

Salovum egg powder high in antisecretory factor, 4 g/sachet. Four sachets, ie 16 g q 8 h for 6 days starting 6 days before 1st cycle of chemotherapy. SPC-flakes flat dose of 75 g/d divided in 2 - 4 doses started in parallel with Salovum to be continued during the first 8 weeks of chemotherapy.

Dietary Supplement: Salovum and SPC-flakes active or placebo

Control

PLACEBO COMPARATOR

Salovum placebo powder without antisecretory factor, 4 g/sachet. Four sachets, ie 16 g q 8 h for 6 days starting 6 days before 1st cycle of chemotherapy. SPC placebo flakes flat dose of 75 g/d divided in 2 - 4 doses started in parallel with Salovum placebo to be continued during the first 8 weeks of chemotherapy.

Dietary Supplement: Salovum and SPC-flakes active or placebo

Interventions

Salovum and SPC-flakes active or placebo DIETARY_SUPPLEMENT

Foods for specific medical purposes or corresponding placebo

Active; Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed diagnosis of colorectal cancer.
• Planned to start 1st line dihydropyrimidine (i e 5-FU or capecitabine) based chemotherapy in the adjuvant, neoadjuvant or palliative setting.
• Planned duration of chemotherapy ≥ 2 months.
• Signed informed consent.
• Liver metastatic disease (pharmacodynamics study only).

You may not qualify if:

• 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.
• 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 5-FU based chemotherapy.
• Prior exposure to Salovum or SPC-flakes.

Sponsors & Collaborators

• Uppsala University Hospital: lead
• Lantmännen AB: collaborator
• Sjöbergstiftelsen: collaborator
• Onkologiska klinikens forskningsfond: collaborator
• Swedish Cancer Society: collaborator

Study Sites (1)

University hospital

Uppsala, 75185, Sweden

RECRUITING

Related Publications (6)

• 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.

  PMID: 20684797 BACKGROUND

• 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.

  PMID: 9414971 BACKGROUND

• Zaman S, Aamir K, Lange S, Jennische E, Silfverdal SA, Hanson LA. Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study. Acta Paediatr. 2014 Jun;103(6):659-64. doi: 10.1111/apa.12581. Epub 2014 Mar 10.

  PMID: 24484450 BACKGROUND

• Bjorck S, Bosaeus I, Ek E, Jennische E, Lonnroth I, Johansson E, Lange S. Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept. Gut. 2000 Jun;46(6):824-9. doi: 10.1136/gut.46.6.824.

  PMID: 10807895 BACKGROUND

• Al-Olama M, Wallgren A, Andersson B, Gatzinsky K, Hultborn R, Karlsson-Parra A, Lange S, Hansson HA, Jennische E. The peptide AF-16 decreases high interstitial fluid pressure in solid tumors. Acta Oncol. 2011 Oct;50(7):1098-104. doi: 10.3109/0284186X.2011.562240. Epub 2011 Mar 4.

  PMID: 21375367 BACKGROUND

• Ilkhanizadeh S, Sabelstrom H, Miroshnikova YA, Frantz A, Zhu W, Idilli A, Lakins JN, Schmidt C, Quigley DA, Fenster T, Yuan E, Trzeciak JR, Saxena S, Lindberg OR, Mouw JK, Burdick JA, Magnitsky S, Berger MS, Phillips JJ, Arosio D, Sun D, Weaver VM, Weiss WA, Persson AI. Antisecretory Factor-Mediated Inhibition of Cell Volume Dynamics Produces Antitumor Activity in Glioblastoma. Mol Cancer Res. 2018 May;16(5):777-790. doi: 10.1158/1541-7786.MCR-17-0413. Epub 2018 Feb 5.

  PMID: 29431617 BACKGROUND

MeSH Terms

Conditions

Diarrhea; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Peter Nygren, MD

CONTACT

+46 70 4250719; peter.nygren@igp.uu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo study products similar to the active products
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in oncology, consultant in oncology

Model Details: Parallel 2 group randomized trial

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 21, 2022
• Study Start: December 15, 2020
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)