Plain English Summary
Background and study aims
Stomatitis (mouth sores) is a common problem for people getting cancer treatment.
To date, no standard preventive measures for stomatitis have been suggested for cancer patients undergoing Everolimus treatment.
Orasol Plus® is a nutritional supplement of the industry, available in liquid form, containing a number of natural components endowed by anti-inflammatory, analgesic and cytoprotective properties. Notably, as per the product data sheet, Orasol Plus® can be swallowed at the end of the rinsing, thus expanding its protective effect not only in the oral cavity, but also in the esophageal mucosa.
The STOmatitis Prevention trial (‘STOP’) is thus aimed at investigating the possibility of using Orasol Plus® in patients with advanced RCC treated with Everolimus, in order to prevent the development of stomatitis of any grade.
Who can participate?
Patients who received Everolimus for cancer treatment.
What does the study involve?
Patients will be asked to practice standard oral hygiene, according to the National Association of Italian Dentists (ANDI) guidelines with or without additional use of Orasol Plus® mouthwash.
What are the possible benefits and risks of participating?
Benefits: expected reduction, in terms of severity and/or duration, the oral stomatitis so frequently observed in cancer patients treated with the oral agent Everolimus
Risks: being a natural compound and not a true drug, we do not expect any significant risk for patients taking part in this study
Where is the study run from?
1. IRCCS San Matteo University Hospital Foundation, Italy
2. IRCCS National Cancer Institute, Italy
3. Santi Antonio e Biagio e C. Arrigo Hospital, Italy
4. Papa Giovanni XXIII Hospital, Italy
5. Spedali Civili, Italy
When is the study starting and how long is it expected to run for?
August 2013 to December 2014
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Prof. Camillo Porta
Trial website
Contact information
Type
Scientific
Primary contact
Prof Camillo Porta
ORCID ID
http://orcid.org/0000-0003-2412-1563
Contact details
Medical Oncology
IRCCS San Matteo University Hospital
Pavia
27100
Italy
+39-0382-592265
camillo.porta@icsmaugeri.it
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
GION 2013-01
Study information
Scientific title
STOP (everolimus-induced STOmatitis Prevention trial) - randomized phase III study to assess the effectiveness of Orasol Plus ™ mouthwashes associated with standard oral hygiene (vs standard oral hygiene) to prevent everolimus-induced stomatitis in patients with advanced renal carcinoma
Acronym
STOP
Study hypothesis
Use of a commercial natural multicomponent mouthwash, in association with standard oral hygiene (vs oral hygiene alone), could prevent everolimus-induced stomatitis in advanced renal cell carcinoma patients
Ethics approval
Approved 06/05/2013, IRCCS San Matteo University Hospital Institutional Review Board (IRB) (Comitato Etico IRCCS Policlinico San Matteo, piazzale C. Golgi 19, 27100 Pavia, Italy; +39-0382-502508; c.fiocchi@smatteo.pv.it), ref: 3DG0764
Study design
Prospective multicentre randomized open-label study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Home
Trial type
Prevention
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Oral stomatitis induced by everolimus treatment
Intervention
‘STOP’ is a prospective, multicentre, randomized (1:1), open-label study, aimed at comparing the incidence and duration of cases of mucositis of any grade in two groups of metastatic renal cell carcinoma patients on everolimus anticancer therapy treated prophylactically with Orasol Plus® in addition to standard oral hygiene, or with standard oral hygiene alone.
Experimental prophylactic treatment consisted of oral mouth rinses with Orasol Plus® mouthwash plus standard oral hygiene, while standard treatment consisted of oral hygiene alone. Based on the Orasol Plus® data sheet, the patients performed three mouth rinses within 24 hours (at least three hours apart from each other), using for each rinsing a measure of undiluted mouthwash: the patient rinsed for at least 30 seconds and then swallowed the product. In order to standardize how the rinses were performed, during the screening visit the patient was carefully instructed in this regard and performed two test rinses (with water) in the presence of the Physician who proposed the protocol.
Standard oral hygiene, according to the National Association of Italian Dentists (ANDI) guidelines, all patients enrolled in the protocol were required to follow and that was adequately explained to them, included the following activities:
1. Brush teeth twice a day and use dental floss daily
2. Use fluoride-containing toothpaste.
In particular, a correct use of the toothbrush involves the following steps:
• Place the toothbrush at an angle of 45 ° against the gingival margin and brush or rotate away from the gingival margin
• Gently brush the outside, the inside and the surface of each tooth with fast forward and backward movements
• Gently brush the tongue to remove bacteria and refresh the breath
A correct use of dental floss involves the following steps:
• Use about 45 cm of thread, rolling it around the middle finger of both hands and leaving a few centimeters to work with
• Gently follow the curves of the teeth
• Be sure to clean under the gum line and avoid hitting them
Randomization:
A randomization list has been generated, which is managed by the Coordinating Center; as a result of the arrival of relative screening card, each individual patient is randomized and the relative outcome of the randomization is communicated directly to each participating Center via fax.
Data collection and follow-up:
Individual patient's data are collected using a paper CRF, a copy of which has to be sent to the Coordinating Center when the patient completes the study or withdraws from it, while the original remains at each single participating center. The study duration, in light of the expected average duration of Everolimus treatment, predictable based on the results of the RECORD-1 pivotal study, the STOP study will have a maximum duration of 150 days; patients who eventually stop treatment before day 150, whether due to toxicity or ineffectiveness of the treatment, will still be included in the analysis. After a maximum of 150 days patients will not be further followed-up for study purposes.
Intervention type
Supplement
Phase
Drug names
Primary outcome measure
Efficacy of Orasol Plus® in addition to standard oral hygiene in the prevention of Everolimus-induced mucositis evaluated through physical examination and patient's interview at T0 (screening), T1 (day +15 from treatment start), T2 (day +30), T3 (day +90) and T4 (day +150/study end).
Secondary outcome measures
All evaluated through physical examination and patient's interview at T0 (screening), T1 (day +15 from treatment start), T2 (day +30), T3 (day +90) and T4 (day +150/study end):
1. Pain and the consequent need for analgesic (NSAIDs, major analgesics, steroids)
2. Incidence of infectious episodes in the oral cavity
3. Evaluation of nutritional status
Overall trial start date
07/05/2013
Overall trial end date
31/12/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients affected by locally advanced and/or metastatic RCC (of any histological subtype), for which a second or third line treatment with Everolimus was provided (as indicated by the Italian Medicines Agency [AIFA])
2. Patients who received Everolimus as part of experimental protocols were included in the present study only if Everolimus was administered as monotherapy (not in combination) and any protocol in question did not explicitly prohibit the use of food supplements; age over 18
3. Written informed consent to join the study
4. ECOG Performance Status of 0, 1 or 2
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
62
Participant exclusion criteria
Poor patient compliance, and ongoing systemic or oral infections
Recruitment start date
01/08/2013
Recruitment end date
31/12/2014
Locations
Countries of recruitment
Italy
Trial participating centre
IRCCS San Matteo University Hospital Foundation
Piazzale Golgi 9
Pavia
27100
Italy
Trial participating centre
IRCCS National Cancer Institute
Via Venezian 1
Milan
20133
Italy
Trial participating centre
Santi Antonio e Biagio e C. Arrigo Hospital
Via Venezia 16
Alessandria
15121
Italy
Trial participating centre
Papa Giovanni XXIII Hospital
Centro Ospedaliero
Bergamo
24129
Italy
Trial participating centre
Spedali Civili
Piazza Spedali Civili 1
Brescia
25123
Italy
Sponsor information
Organisation
Italian Nephro-Oncology Group (GION)
Sponsor details
via Liutprando 9
Pavia
27100
Italy
+39-335-6230539
camillo.porta@gmail.com
Sponsor type
Charity
Website
Funders
Funder type
Other
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Final study results to be published as a full paper on an international peer-reviewed journal
IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository. The dataset of the present study is stored in the database of all the studies conducted by the STOP trial's Sponsor, i.e. the Italian Group of Onconephrology/Gruppo Italiano di Onco-Nefrologia (GION). Anonymised data will be available from the time of study results' publication for a period of two years for possible audit purposes from Regulatory authorities, provided a formal request for data access. Patients authorized this use of collected data signing study's informed consent.
Intention to publish date
15/08/2019
Participant level data
Available on request
Basic results (scientific)
Publication list