Condition category
Digestive System
Date applied
15/07/2019
Date assigned
02/08/2019
Last edited
29/08/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Publication citations

Additional files

Editorial Notes

29/08/2019: Internal review. 01/08/2019: Trial’s existence confirmed by IRCCS San Matteo University Hospital Institutional Review Board.