Role of Antisecretory Factor in Curative Radiochemotherapy for Anal Carcinoma (SALFLAC)
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
調査の概要
詳細な説明
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).
研究の種類
入学 (予想される)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前:Peter Nygren, MD
- 電話番号:+46704250719
- メール:peter.nygren@igp.uu.se
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ:SPC-flakes with or without Salovum
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.
|
Salovum and SPC-flakes are foods approved for specific medical purposes.
|
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プラセボコンパレーター:SPC-flakes placebo with or without Salovum placebo
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.
|
Salovum and SPC-flakes are foods approved for specific medical purposes.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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.
時間枠:Through study completion, approximately 6 months
|
Treatment related toxicity
|
Through study completion, approximately 6 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence and severity of other AEs according to CTCAEv5.0 during and up to 6 months after RCT.
時間枠:Through study completion, approximately 6 months
|
Other treatment related toxicity
|
Through study completion, approximately 6 months
|
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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.
時間枠:Through study completion, approximately 6 months
|
PROMS
|
Through study completion, approximately 6 months
|
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Increase in plasma (P)-ASF concentration from baseline to the day of start of RCT and to the end of treatment.
時間枠:Days -1, 6 and 42
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Pharmacodynamic outcome and compliance check
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Days -1, 6 and 42
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Relationships between P-ASF concentration, biomarkers reflecting inflammation and adverse events.
時間枠:Through study completion, approximately 6 months
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Biomarker assessments
|
Through study completion, approximately 6 months
|
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Differences in primary and secondary endpoints between Salovum and placebo subgroups.
時間枠:Through study completion, approximately 6 months
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Assessment of added value of Salovum
|
Through study completion, approximately 6 months
|
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Tumour response rate according to RECIST v1.1 and clinical examination at 2, 3 (radiology) and 6 months after stop of RCT.
時間枠:Through study completion, approximately 6 months
|
Assessment of benefit, if any, from study products on clinical outcome
|
Through study completion, approximately 6 months
|
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Disease free and overall survival at 3 and 6 months after stop of RCT.
時間枠:At 3 and 6 months after stop of treatment
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Assessment of benefit, if any, from study products on clinical outcome
|
At 3 and 6 months after stop of treatment
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of AEs CTCAEv5.0 grade ≥ 2 considered probably related to investigational products/placebo.
時間枠:Through study completion, approximately 6 months
|
Adverse effects from study products
|
Through study completion, approximately 6 months
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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研究の完了 (予想される)
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