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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 183
- 试验地点
- 50
- 主要终点
- Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Clonidine Lauriad® 50µg
50µg muco-adhesive buccal tablets, once de day, every day up to 8 weeks
干预措施: Clonidine Lauriad® 50µg (Drug)
Clonidine Lauriad® 100µg
100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks
干预措施: Clonidine Lauriad® 100µg (Drug)
Placebo Lauriad®
Placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks
干预措施: Placebo Lauriad® (Drug)
结局指标
主要结局
Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed
时间窗: 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.
次要结局
- Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation)(8 weeks)
- Overall Survival(2 years)
- At Least One Opioid Use (Class 3 Analgesic)(8 weeks)
- Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range)(8 weeks)