Clinical trial NCT01385748: Efficacy and Safety Study of Clonidine Lauriad® to Treat Oral Mucositis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Oral Mucositis
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-06-30
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed
timeFrame: 8 weeks
Secondary outcomes:
measure: At Least One Opioid Use (Class 3 Analgesic)
timeFrame: 8 weeks
measure: Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation)
timeFrame: 8 weeks
measure: Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range)
timeFrame: 8 weeks
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
measure: Time to Onset of Severe Oral Mucositis
timeFrame: 8 weeks
measure: The Maximum Severity of Oral Mucositis
timeFrame: 8 weeks
measure: The Overall Incidence of Grade 3/4 Mucositis During the Active Phase.
timeFrame: 8 weeks
measure: Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher
timeFrame: 8 weeks
measure: Overall Treatment Compliance According to the Patient Diary
timeFrame: 8 weeks
Locations:
city: Sun City
country: United States
facility: 21st Century Oncology of Arizona
state: Arizona
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Researche and Excellence
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corp.
state: California
city: Denver
country: United States
facility: Centura Health Research Center
state: Colorado
city: Farmington
country: United States
facility: University of Connectcut Health Center
state: Connecticut
city: Miami
country: United States
facility: AMPM Research Clinic
state: Florida
city: Detroit
country: United States
facility: Barbara Ann Karmonos Cancer Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of medecine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Montana
state: Montana
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center- Carolinas Health Care System
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institut
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Besançon
country: France
facility: Hospital Jean Minjoz
city: Brest
country: France
facility: CHU Morvan
city: Caen
country: France
facility: Centre François Baclesse
city: Evreux
country: France
facility: Clinique Pasteur
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Clinique Chénieux
city: Neuilly-sur-Seine
country: France
facility: Clinique Hartmann
city: Pierre-Bénite
country: France
facility: CH Lyon Sud
city: Poitiers
country: France
facility: CHU La Milétrie
city: Saint gregoire
country: France
facility: CHP St gregoire
city: Saint-Nazaire
country: France
facility: Centre de Cancérologie Etienne-Dolet
city: Tours
country: France
facility: Hôpital Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen Strahlenklinik
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg Klinik fur Strahlentherapie
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Osnabruck
country: Germany
facility: Paracelsius- Klinik
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza
state: Nyíri u. 38
city: Nyíregyháza
country: Hungary
facility: Jósa András Oktatókórház Egészségügyi Szolgáltató Nonprofit Kft.
state: Szent István út 68
city: Miskolc,
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
state: Szentpéteri kapu 72-76
city: Budapest
country: Hungary
facility: Szent Imre Kórház
state: Tétényi út 12-16.
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario de La princesa
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de octubre
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y cajal
city: Malaga
country: Spain
facility: Hospital Carlos Haya
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire
Study officials:
affiliation: Valerio Therapeutics
name: Bérangère Vasseur, MD
role: STUDY_DIRECTOR
References: