Neoplasms

All Conditions

Mouth and Tooth Diseases

Digestive System Diseases

Head and Neck Neoplasms

Stomatitis

Mucositis

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Antihypertensive Agents

Analgesics

All Drugs and Chemicals

Clonidine

Sympatholytics

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

50µg muco-adhesive buccal tablets, once de day, every day up to 8 weeks

100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks

Placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks

50µg muco-adhesive buccal tablet once day every day up to 8 weeks

Clonidine Lauriad® 50µg

Clonidine Lauriad® 100µg

placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks

Placebo Lauriad®

Bérangère Vasseur, MD

The purpose of this study is to evaluate the efficacy and safety of Clonidine Lauriad® to treat chemoradiation therapy induced severe oral mucositis in patients with head and neck cancer.

Efficacy and Safety Study of Clonidine Lauriad® to Treat Oral Mucositis

A Phase II, Multi-center, Randomised, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Lauriad® 50 μg and 100 μg Mucoadhesive Buccal Tablet (MBT) Applied Once Daily to Those of Placebo in the Prevention and Treatment of Chemoradiation Therapy Induced Oral Mucositis in Patients With Head and Neck Cancer

Time to onset is the duration until first Severe Oral Mucositis. Severe Oral Mucositis was defined as a Grade 3 or Grade 4 score on the World Health Organization (WHO) oral mucositis severity scale. Participants were assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible.

Participants were assessed using the World Health Organization (WHO) oral mucositis severity scale twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. The WHO scores were as follows: 0 = None; 1 = oral soreness, erythema; 2 = oral erythema, ulcers, solid diet tolerated; 3 = oral ulcers, liquid diet only; 4 = oral alimentation impossible. The maximum severity was the maximum score reported during the active phase.

The presence of grade 3 or 4 oral mucositis on the World Health Organization (WHO) oral mucositis severity scale was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible.The number of participants with at least one Grade 3 or Grade 4 mucositis score during the active phase is reported.

Salivary flow was assessed and scored by the investigator weekly using the NCI-CTC scale for xerostomia for up to 8 weeks during the active phase (radiotherapy). Time to appearance of Grade 2 or higher on the following 4-point scoring scale is reported: 0 = normal; 1 = symptomatic (dry or thick saliva) without significant dietary alteration (unstimulated saliva flow greater than 0.2 mL/minute); 2 = symptomatic and significant oral intake alterations (e.g. copious water, other lubricants, diet limited to purees and/or soft, moist foods) (unstimulated saliva 0.1 to 0.2 mL/minute); and 3 = symptoms leading to inability to adequately aliment orally, intravenous fluids, tube feedings, or total parenteral nutrition indicated (unstimulated saliva \< 0.1 mL/minute).

All participants complete a daily questionnaire during the active phase (radiotherapy). Compliance = \[ number of tablets / (end date of treatment - start date treatment + 1 ) \] \* 100. The "number of tablets" is the number of days with a tablet applied and treatment start and end dates are the first and last dates of the patient diary with a tablet applied.

The primary endpoint planned in the protocol was the percentage of participants with an oral mucositis score greater than or equal to 3 using the WHO oral mucositis severity scale at a cumulative radiation dose of 50 Gy. This was modified by protocol amendment to the cumulative radiation dose at which a WHO score greater than or equal to 3 was first observed. This change was made to account for the fact that in real practice most patients receive a cumulative dose between 60 and 70 Gy. The presence of grade 3 or 4 oral mucositis was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = oral ulcers, liquid diet only; WHO score 4 = oral alimentation impossible. Each assessment was associated with the actual cumulative dose of radiotherapy.

Opioid use was recorded twice weekly during the active phase (radiotherapy)

Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported.

After the end-of study visit, the investigator center collects OS follow-up data for each patient who has consented to participate in the follow-up data collection. the OS follow-up period was still ongoing at time of the primary analysis and ended in Nov 2016. The analysis was condicted on the ITT population. The overall survival was evaluate every 6 months after last subject completed in patients who has consented to participate .

Valerio Therapeutics

Two of the 183 participants received study treatment but withdrew early without any safety assessments (1 in the clonidine Lauriad 50 μg group and 1 in the clonidine Lauriad 100 μg group). The safety population therefore included 181 participants.

Clonidine Lauriad® 50µg: 50µg muco-adhesive buccal tablet once a day every day up to 8 weeks

Clonidine Lauriad® 100µg: 100µg muco-adhesive buccal tablets once a day every day up to 8 weeks

Placebo Lauriad®: placebo muco-adhesive buccal tablets, once a day every day up to 8 weeks

Pooled group of participants who received Clonidine Lauriad® 50 ug muco-adhesive buccal tablets or Clonidine Lauriad® 100 ug muco-adhesive buccal tablets once a day every day up to 8 weeks

Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled

Clonidine Lauriad® 50 µg: 50µg muco-adhesive buccal tablet once a day every day up to 8 weeks

Clonidine Lauriad® 50 µg

Clonidine Lauriad® 100 µg: 100µg muco-adhesive buccal tablets once a day every day up to 8 weeks

Clonidine Lauriad® 100 µg

Total

Age, Continuous

18 to 64 years

65 to 84 years

85 years and over

Age, Customized

Sex: Female, Male

Caucasian

Other

Black

Race/Ethnicity, Customized

Hungary

United States

France

Switzerland

Germany

Spain

Region of Enrollment

Score 0

Score 1

Score 2

ECOG performance status measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50% of waking hours), capable of all self care, unable to carry out any work activities; 3=Capable of only limited self care, confined to bed/chair \>50% of waking hours; 4=Completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=Dead.

Eastern Cooperative Oncology Group (ECOG) Score

Oral cavity

Oropharynx

Hypopharynx

Larynx

Oral cavity/oropharynx

Oral cavity/hypopharynx

Oral cavity/larynx

Oropharynx/hypopharynx

Oropharynx/larynx

The location of the squamous cell carcinoma.

Disease location

Location of the squamous cell carcinoma (in oral cavity or oropharynx).

Disease location in oral cavity or oropharynx

Missing

The number of participants with mucosal irritation at baseline.

Mucosal irritation

The number of participants having undergone tooth extraction at baseline.

Tooth extraction

The number of participants presenting with oral infection at baseline.

Oral infection

The number of participants having undergone prior surgery.

Prior surgery

The number of participants previously treated with radiotherapy and/or chemotherapy.

Prior radiotherapy and/or chemotherapy

Height

Weight

Body Mass Index (BMI)

Duration of the squamous cell carcinoma at baseline.

Disease duration

Berangere Vasseur, MD

Clonidine Lauriad® 50 µg: 50 µg muco-adhesive buccal tablet once a day every day up to 8 weeks

Clonidine Lauriad® 100 µg: 100 µg muco-adhesive buccal tablets once a day every day up to 8 weeks

Placebo Lauriad®: placebo muco-adhesive buccal tablets once a day every day up to 8 weeks

Pooled group of participants who received Clonidine Lauriad® 50 ug muco-adhesive buccal tablets or Clonidine Lauriad® 100 ug muco-adhesive buccal tablets once a day every day up to 8 weeks.

The analysis was conducted on the Intent to treat population, defined as all participants who received at least one dose of investigational drug.

Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed

At Least One Opioid Use (Class 3 Analgesic)

Participants with at least one use of an opioid during the active phase with evaluable data.

Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation)

Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range)

The population for the 2-year OS follow-up was the ITT defined as all patients who received at least 1 dose of investigational drug.

Overall Survival

Time to Onset of Severe Oral Mucositis

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

No value during the concerned period

The Maximum Severity of Oral Mucositis

Missing = participants without a WHO score during the active phase

Spots Global Cancer Trial Database for placebo lauriad®