Efficacy and Safety Study of Clonidine Lauriad® to Treat Oral Mucositis
- Conditions
- Oral Mucositis
- Interventions
- Registration Number
- NCT01385748
- Lead Sponsor
- Valerio Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 183
-
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:
- 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.
- 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:
- Haemoglobin ≥ 10g/dL
- Absolute neutrophil counts ≥ 1500 cells/mm3
- Platelets ≥ 100.000/mm3
- Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN)
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN
- Negative serum pregnancy test
-
Women of child bearing potential must have effective contraception method (oral or device)
-
Signed written informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Clonidine Lauriad® 100µg Clonidine Lauriad® 100µg 100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks Placebo Lauriad® Placebo Lauriad® Placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks Clonidine Lauriad® 50µg Clonidine Lauriad® 50µg 50µg muco-adhesive buccal tablets, once de day, every day up to 8 weeks
- Primary Outcome Measures
Name Time Method Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed 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
Name Time Method Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) 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.
Overall Survival 2 years 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 .
At Least One Opioid Use (Class 3 Analgesic) 8 weeks Opioid use was recorded twice weekly during the active phase (radiotherapy)
Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) 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.
Trial Locations
- Locations (50)
Carolinas Medical Center- Carolinas Health Care System
🇺🇸Charlotte, North Carolina, United States
Clinique Pasteur
🇫🇷Evreux, France
21st Century Oncology of Arizona
🇺🇸Sun City, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
Barbara Ann Karmonos Cancer Hospital
🇺🇸Detroit, Michigan, United States
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Clinique Chénieux
🇫🇷Limoges, France
CH Lyon Sud
🇫🇷Pierre-Bénite, France
Central Coast Medical Oncology Corp.
🇺🇸Santa Maria, California, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
California Cancer Associates for Researche and Excellence
🇺🇸Fresno, California, United States
Penn State Hershey Cancer Institut
🇺🇸Hershey, Pennsylvania, United States
Compassionate Cancer Care Medical Group
🇺🇸Riverside, California, United States
Centura Health Research Center
🇺🇸Denver, Colorado, United States
Washington University School of medecine
🇺🇸Saint Louis, Missouri, United States
CHU Morvan
🇫🇷Brest, France
Hospital Jean Minjoz
🇫🇷Besançon, France
Universitatsklinikum Freiburg Klinik fur Strahlentherapie
🇩🇪Freiburg, Germany
Jósa András Oktatókórház Egészségügyi Szolgáltató Nonprofit Kft.
🇭🇺Nyíregyháza, Szent István út 68, Hungary
Hospital Universitario de La princesa
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital 12 de octubre
🇪🇸Madrid, Spain
Hospital Puerta de Hierro Majadahonda
🇪🇸Madrid, Spain
Hospital Universitario Ramon y cajal
🇪🇸Madrid, Spain
Hospital Carlos Haya
🇪🇸Malaga, Spain
Hospital de Navarra
🇪🇸Pamplona, Spain
Hospital Virgen de la Victoria
🇪🇸Malaga, Spain
Centre Hospitalier Universitaire
🇨🇭Lausanne, Switzerland
University of Connectcut Health Center
🇺🇸Farmington, Connecticut, United States
AMPM Research Clinic
🇺🇸Miami, Florida, United States
Centre Oscar Lambret
🇫🇷Lille, France
Centre François Baclesse
🇫🇷Caen, France
Billings Clinic Montana
🇺🇸Billings, Montana, United States
Clinique Hartmann
🇫🇷Neuilly-sur-Seine, France
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
CHU La Milétrie
🇫🇷Poitiers, France
Paracelsius- Klinik
🇩🇪Osnabruck, Germany
Universitatsklinikum Erlangen Strahlenklinik
🇩🇪Erlangen, Germany
CHP St gregoire
🇫🇷Saint gregoire, France
Hôpital Bretonneau
🇫🇷Tours, France
Centre de Cancérologie Etienne-Dolet
🇫🇷Saint-Nazaire, France
Szent Imre Kórház
🇭🇺Budapest, Tétényi út 12-16., Hungary
Institut Gustave Roussy
🇫🇷Villejuif, France
Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
🇭🇺Miskolc,, Szentpéteri kapu 72-76, Hungary
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza
🇭🇺Kecskemét, Nyíri u. 38, Hungary
Montefiore Medical Center
🇺🇸The Bronx, New York, United States