A Randomized, Open-label, Phase III Trial to Assess the Efficacy and Safety of BupiZenge Compared to Lidocaine for Pain Associated With Oral Mucositis in Head and Neck Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 12
- 主要终点
- Total pain reduction in oral cavity pain over 3 hours after taking study treatment on the last day of radiotherapy
研究概览
简要总结
Most patients who receive radiation therapy for head and neck cancer develop painful sores in the mouth called oral mucositis. For many of them, these sores are severe and result in debilitating pain. The sores usually start in the third week of radiation and last aboutfive weeks, often continuing for two weeks after treatment ends. Current pain treatments, for instance lidocaine solution, only give short-lasting pain relief.
BupiZenge is a lozenge that dissolves slowly in the mouth and contains bupivacaine. Bupivacaine is a long-acting pain-relieving medicine and has been safely used for many years for both children and adults, and its safety profile is well understood. The BupiZenge lozenge is designed to give longer and more reliable pain relief for patients with mucositis in their mouth.
This study will check if BupiZenge works better to reduce pain than lidocaine, and if better pain control improves quality of life and reduces the need for strong pain medicines like opioids.
The main goal is to see how much mouth pain decreases after taking BupiZenge compared to lidocaine. This is measured by asking the patients to rate their pain score on a scale from 0 (no pain) to 10 (worst possible pain). This is done at different time-points, from before the dose until three hours after dose on the last day of radiotherapy.
The study will include 150 adults, both women and men, aged 18 to 80 years, who have head and neck cancer and are scheduled to receive radiotherapy, with or without chemotherapy. These patients will be randomly assigned to one of the treatment groups. The first is BupiZenge, which is a lozenge containing bupivacaine, which dissolves slowly in the mouth. The second is lidocaine, which is a liquid solution for use in the mouth that you gurgle or swish around in the mouth.
The study begins with a combined screening and run-in period that can last up to five weeks. During radiotherapy, patients record their mouth pain each day using a number scale from 0 (no pain) to 10 (worst possible pain). If the pain score is at least 4 (moderate pain) and they have developed mucositis in the mouth within 5 weeks, patients are randomly assigned to receive either BupiZenge or Lidocaine.
Treatment continues at least until radiotherapy is completed. If the patient has pain and mouth sores, and the treatment is working well, it may continue after radiotherapy ends, but only until the sores heal or for a maximum of six weeks in total, whichever occurs first. After treatment ends, there is a 30-day follow-up period.
详细描述
Pharmacokinetic (PK) parameters of bupivacaine in plasma will be evaluated in a sub-trial including participants randomized to the BupiZenge treatment arm.
Approximately 15 participants (no more than 25), across all designated PK sites, will participate in a PK sub-trial. Blood samples will be collected before the dose and at scheduled time points up to three hours after the dose for PK evaluation. Samples will be analyzed by a central laboratory, and results will be reported to the Sponsor or Sponsor's designee during the course of the trial. Overall, the PK sub-group represents a targeted, ethical, and efficient approach to verify systemic safety parameters for BupiZenge in the intended patient population.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must provide signed written informed consent prior to trial participation and must be willing and able to comply with all requirements and restrictions of the trial.
- •Male or female aged ≥ 18 on the day of consent and ≤ 80 on the first day of dosing.
- •Pathologically confirmed diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or nasopharynx.
- •About to start IMRT with curative intent with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative intended dose of at least 60 Gy and a maximum of 72 Gy. Proton therapy given at equivalent biological doses is allowed.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Female participants of childbearing potential (WOCBP) must agree to use a highly effective contraceptive measure or practice total sexual abstinence from the time of giving informed consent until at least 24 hours after last dose of IMP.
排除标准
- •Participation in another investigational interventional clinical trial within 3 months prior to first dosing, or for a longer period if required by local regulations, or within 5 half-lives of the investigational agent taken (whichever is longer). An exception is studies where patients are randomized to different radiotherapy settings, e.g. participation in DAHANCA 35 is allowed.
- •Previous radiation therapy to the head and/or neck area.
- •Pre-existing OM, active herpes simplex virus (HSV) infection, or untreated or uncontrolled oral candidiasis.
- •Receiving high-dose (> 15 mg per day prednisolone), corticosteroids (for any indication).
- •Known allergy or intolerance to bupivacaine, lidocaine, or any of the excipients in the products.
- •Significant cardiac disease such as AV block II-III or requiring treatment with antiarrhythmic drugs in class III (e.g., amiodarone).
- •Inability to eat or drink, or dependence on an enteral feeding tube (percutaneous endoscopic gastrostomy [PEG] or nasogastric tube) for any reason.
- •Moderate/severe liver or kidney disease defined as:
- •AST/ALT > 3 × upper limit of normal (ULN) or bilirubin > 1.5 × ULN (unless related to Gilbert's syndrome)
- •glomerular filtration rate (GFR) < 30 mL/min/1.73 m2
- •Known diagnosis of epilepsy.
- •Known phenylketonuria (PKU).
- •Pregnancy or breastfeeding.
- •Any condition or circumstance-based on the investigator's assessment-that could increase risk to the participant, confound trial results, or interfere with compliance / participation (including inability or unwillingness to follow trial procedures, or any clinically significant physical or psychiatric condition).
研究组 & 干预措施
BupiZenge
Bupivacaine hydrochloride, 25 mg lozenge
干预措施: BupiZenge 25 mg (Drug)
Lidocaine
Lidocaine hydrochloride oral topical solution, 20 mg/mL
干预措施: Lidocaine viscous 2% (Drug)
结局指标
主要结局
Total pain reduction in oral cavity pain over 3 hours after taking study treatment on the last day of radiotherapy
时间窗: From before to 3 hours after dose, on the last day of radiotherapy
Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Participants will rate their pain before taking the study treatment and at several time points after dosing. These measurements will be combined to assess how pain changes over time after treatment and to compare BupiZenge with lidocaine.
次要结局
- Total pain reduction in oral cavity pain over 3 hours after taking study treatment(From before dose to 3 hours after dose, on Day 1 and during Weeks 1 to 3)
- Proportion of patients with meaningful pain reduction over 3 hours after taking study treatment(From before dose to 3 hours after dose, on the last day of radiotherapy and during Weeks 1 to 3)
- Change in oral cavity pain 15 minutes after taking study treatment(From before dose to 15 minutes after dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy)
- Change in oral cavity pain 60 minutes after taking study treatment(From before dose to 60 minutes after dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy)
- Change in oral cavity pain from Day 1 before dose to later pre-dose assessments(From before dose (Day 1) to before dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy)
- Safety as measured frequency and severity of adverse events(From signature of informed consent up to 30 days after treatment discontinuation)
- Change from baseline in hematology laboratory parameters.(From informed consent to 30 days after treatment discontinuation.)
- Change from baseline in chemistry laboratory parameters.(From informed consent to 30 days after treatment discontinuation.)
- Changes from baseline in body weight(From signature of informed consent up to 30 days after treatment discontinuation)
- Changes from baseline in blood pressure.(From signature of informed consent up to 30 days after treatment discontinuation)
- Changes from baseline in heart rate.(From signature of informed consent up to 30 days after treatment discontinuation)
- Changes from baseline in body temperature .(From signature of informed consent up to 30 days after treatment discontinuation)
- Changes from baseline in respiratory rate.(From signature of informed consent up to 30 days after treatment discontinuation)
- Tolerability as measured by dose modifications due to adverse events(From signature of informed consent up to 30 days after treatment discontinuation)
- Adverse Events related to local tolerability in the oral cavity, as assessed by CTCAE v6.0, will be summarized.(From Week 2 up to Week 5.)
- Oral intake of opioids during the treatment period with concomitant BupiZenge/lidocaine treatment and radiotherapy comparing BupiZenge with lidocaine.(From randomization up to Week 5.)
- Time (days) to start of opioid medication during radiotherapy comparing BupiZenge with lidocaine(From randomization up to Week 5.)
- Change in Modified Oral Mucositis Daily Questionnaire (mOMDQ) Total Score(From randomization up to Week 5.)
- Quality-of-life measured as change from baseline using RAND SF-36 questionnaire(From randomization up to Week 5.)
- Progression of oral mucositis from WHO Grade 2 to Grade 3 or higher(From randomization up to Week 5.)
- Maximum Plasma Concentration [Cmax] of bupivaccaine in plasma.(Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period)
- Time to maximum Plasma Concentration [Tmax] of bupivaccaine in plasma.(Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period)
- Area under the plasma concentration-time curve from time zero to 3 hours after dose (AUC0-3h)(Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period)
- Health Resource Utilization Questionnaire (HRUQ) Total Score at 30 days after treatment(Assessed 30 days after end of treatment)
- Change in Work Productivity and Activity Impairment (WPAI) Total Score from baseline to 30 days after treatment(From screening to 30 days after end of treatment)