We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01385748
First Posted: June 30, 2011
Last Update Posted: August 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Onxeo
  Purpose
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.

Condition Intervention Phase
Oral Mucositis Drug: Clonidine Lauriad® 50µg Drug: Clonidine Lauriad® 100µg Drug: Placebo Lauriad® Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Onxeo:

Primary Outcome Measures:
  • Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed [ Time Frame: 8 weeks ]
    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.


Secondary Outcome Measures:
  • At Least One Opioid Use (Class 3 Analgesic) [ Time Frame: 8 weeks ]
    Opioid use was recorded twice weekly during the active phase (radiotherapy)

  • Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) [ Time Frame: 8 weeks ]
    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.

  • Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) [ Time Frame: 8 weeks ]
    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.


Other Outcome Measures:
  • Time to Onset of Severe Oral Mucositis [ Time Frame: 8 weeks ]
    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.

  • The Maximum Severity of Oral Mucositis [ Time Frame: 8 weeks ]
    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 Overall Incidence of Grade 3/4 Mucositis During the Active Phase. [ Time Frame: 8 weeks ]
    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 Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher [ Time Frame: 8 weeks ]
    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).

  • Overall Treatment Compliance According to the Patient Diary [ Time Frame: 8 weeks ]
    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.


Enrollment: 183
Study Start Date: April 2010
Study Completion Date: December 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Clonidine Lauriad® 50µg
50µg muco-adhesive buccal tablets, once de day, every day up to 8 weeks
Drug: Clonidine Lauriad® 50µg
50µg muco-adhesive buccal tablet once day every day up to 8 weeks
Active Comparator: Clonidine Lauriad® 100µg
100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks
Drug: Clonidine Lauriad® 100µg
100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks
Placebo Comparator: Placebo Lauriad®
Placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks
Drug: Placebo Lauriad®
placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female
  • Aged > 18 years
  • Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery
  • Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade > 2 oral mucositis during the neoadjuvant therapy.
  • Patient eligible to receive concurrent chemo-radiation defined as:

    1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles.
    2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Screening laboratory tests:

    1. Haemoglobin ≥ 10g/dL
    2. Absolute neutrophil counts ≥ 1500 cells/mm3
    3. Platelets ≥ 100.000/mm3
    4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
    5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
    6. Negative serum pregnancy test
  • Women of child bearing potential must have effective contraception method (oral or device)
  • Signed written informed consent

Exclusion Criteria:

  • Tumours of the lips, sinuses, salivary glands
  • Prior radiation of the head and neck area
  • Curative surgery less than 2 weeks or more than 15 weeks prior to the initiation of radiation therapy-chemotherapy (RT-CT)
  • Presence of active infectious disease
  • Presence of active oral infectious disease, including oropharyngeal candidiasis and/or orofacial herpes
  • Presence of oral mucositis
  • Known or suspected chronic viral diseases including HIV
  • Systolic blood pressure < 100 mmHg and/or Diastolic blood pressure < 50 mmHg
  • Recent stroke within the last 6 months
  • Bradyarrhythmia (<60 b/min), including sinus node dysfunction or atrioventricular (AV) nodal conduction block 2nd or 3rd degree
  • Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up
  • Renal insufficiency (creatinine blood level > 1.5ULN)
  • Ongoing heavy alcohol consumption (>100g alcohol/day)
  • Administration of any concomitant treatment likely to interfere with clonidine
  • Known hypersensitivity to clonidine, history of allergy or intolerance to milk proteins or any other component of the product
  • Presence of severe or uncontrolled depression
  • Pregnant or breast-feeding women
  • Inability to give informed consent or comply with study requirements
  • Unable or unwilling to comply with follow-up visits
  • Participation to a clinical trial within 30 days prior to randomization and during the entire duration of the study
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01385748


  Show 51 Study Locations
Sponsors and Collaborators
Onxeo
Investigators
Study Director: Bérangère Vasseur, MD Onxeo
  More Information

Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT01385748     History of Changes
Other Study ID Numbers: BA2009/28/01
First Submitted: June 29, 2011
First Posted: June 30, 2011
Results First Submitted: October 27, 2016
Results First Posted: August 9, 2017
Last Update Posted: August 9, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Mucositis
Stomatitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
Clonidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action