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

Phase 2

Completed

Conditions: Oral Mucositis

Interventions: Drug: Clonidine Lauriad® 100µg
Drug: Placebo Lauriad®
Drug: Clonidine Lauriad® 50µg

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

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

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): 21st Century Oncology of Arizona
🇺🇸
Sun City, Arizona, United States
Compassionate Cancer Care Medical Group
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Riverside, California, United States
City of Hope
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Duarte, California, United States
California Cancer Associates for Researche and Excellence
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Fresno, California, United States
Central Coast Medical Oncology Corp.
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Santa Maria, California, United States
Centura Health Research Center
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Denver, Colorado, United States
University of Connectcut Health Center
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Farmington, Connecticut, United States
AMPM Research Clinic
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Miami, Florida, United States
Barbara Ann Karmonos Cancer Hospital
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Detroit, Michigan, United States
Washington University School of medecine
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Saint Louis, Missouri, United States
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21st Century Oncology of Arizona
🇺🇸Sun City, Arizona, United States