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

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.

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