Multi-centre, Double-blind, Randomized-controlled Trial to Study the Efficacy and Safety of Gabapentin to Reduce Strong Opioid Use in Treatment of Radiation-induced Pain in Head and Neck Cancer Patients During Curative Radio(Chemo)Therapy.
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Requirement of patients included in 7-week curative radio(chemo)therapy for a (dose-escalation of) strong opioid
研究概览
简要总结
A multi-centre, double-blind, randomized-controlled trial to study the efficacy and safety of gabapentin to reduce the need for strong opioid use in the treatment of radiation-induced pain in head and neck cancer (HNCA) patients undergoing a curative 7-week radio(chemo)therapy course with curative intent. The aim of this study is to establish if addition of gabapentin is more effective in reducing the need to start (or dosage-increase) a strong opioid for HNCA pain than a matching placebo additional to standard pain management (WHO-ladder step 2 and 3).
详细描述
Although pain is a major symptom in head and neck cancer (HNCA) patients, few studies focus on pain management in this population. Current optimal HNCA pain control usually requires the use of a strong opioid (WHO-ladder step 3), increasing the risk of opioid side effects and toxicities. Gabapentin, originally an anticonvulsant drug, has been effectively used off-label to treat multiple neuropathic pain syndromes such as cancer pain, and has been suggested to reduce the need for high doses of strong opioids in HNCA patients under radio(chemo)therapy. A multi-centre, phase III, double-blind, randomised-controlled trial will be set up randomising patients between the experimental group (E) receiving gabapentin, or the control group (C) receiving a matching placebo, both in addition to standard analgesic therapy (steps 2 and 3 on WHO-ladder). The investigators aim to establish if addition of gabapentin is more effective in reducing the need to start (or dosage-increase) a strong opioid for HNCA pain than a matching placebo additional to standard pain management (WHO-ladder step 2 and 3), in HNCA patients scheduled for a curative 7-week radio(chemo)therapy course.
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)
盲法说明
Both patient groups will receive gabapentin or a matching placebo additional to the standard analgesic therapy, and will be asked to consume the content following the predefined directions provided to them. Both the investigators and the patients will be blinded for the IMP, since gabapentin and the matching placebo will appear identical.
The clinical pharmacist responsible for clinical trials as well as Bimetra clinics will receive a sealed envelope from the statistician with the information necessary for decoding.
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
- •Histologically confirmed squamous cell carcinoma of the head and neck region, generally cancer of the oral cavity, pharynx and larynx. Cancer of the nasal cavity, nasopharynx, paranasal sinuses, parotid gland, or a T1-2N0M0 of the glottis are excluded.
- •Primary cancer eligible for primary or adjuvant radiotherapy with or without systemic treatment, with curative intent
- •TNM stage I to IVb, without distant metastases
- •Patients should require the intake of at least a weak opioid (inclusion starting at prescription/intake of at least a step 2 drug (e.g. a step 2 or step 3 analgesic; if a physician would decide to skip step 2) according to the WHO pain ladder)
- •Patients should be 18 or older at the time of enrolment
- •Patients should be able to adequately communicate in Dutch or French
排除标准
- •Patients younger than 18 years at the time of enrolment
- •Patients with cancer of the nasal cavity, nasopharynx, paranasal sinuses, parotid glands, or a T1-2N0M0 of the glottis
- •Pregnant or lactating women (Non-pregnancy must be confirmed before the first administration by use of a urine pregnancy test. Any positive urine pregnancy test must be confirmed via a serum β-HCG test).
- •Patients presenting with another non-cured cancer (e.g. PSA or CEA not within normal range as determined by the treating physician)
- •Patients with a prior history of cancer, with or without radio(chemo)therapy, diagnosed within the last 5 years
- •Patients who report post-operative pain, as judged by the investigator
- •Patients with a locoregional relapse of a prior head and neck tumour, for which they already received surgery or radio(chemo)therapy
- •Patients who received radiation therapy in the head and neck region in the past
- •Patients with (severe) dementia (DSM-IV criteria) or other significant psychiatric illnesses (e.g. mania, psychosis, schizophrenia, Korsakov, diagnosed major depression and/or history of suicide attempts) that would preclude study compliance
- •Patients taking gabapentin/pregabalin or with prior gabapentin/pregabalin use
- •Patients taking pain medications (e.g. topical analgesics such as lidocaine gel or lidocaine patch) for pre-existing pain of other aetiology. Administration of topical mouthwash is allowed.
- •Patients with pre-existing peripheral neuropathy of another aetiology, B12 deficiency, AIDS, monoclonal gammopathy, diabetes, heavy metal poisoning, syphilis, amyloidosis, hyper- or hypothyroidism, inherited neuropathy
- •Patients taking anti-epileptics for (myoclonic) seizures or neuropathic pain
- •Patients taking anti-depressants for neuropathic pain (i.e. anti-depressant described as the first and second group in the BCFI are excluded, anti-depressants of the third group or selective serotonin reuptake inhibitors (SSRI) are allowed)
- •Patients with chronic kidney failure (creatinine clearance <30 ml/min)
- •Patients with a diagnosis of acute pancreatitis within the last 6 months
- •Patients with a current active hepatic or biliary disease
- •Patients presenting with clinical signs of CNS depression
- •Patients with a hypersensitivity to the active substance
- •Patients with galactose intolerance and/or lactase deficiency
研究组 & 干预措施
Experimental group
Patients randomised to the experimental group will receive a prescription for a gabapentin starting dose of 100 mg three times a day (ter in die, t.i.d) /day per orally, additional to the analgesics according to standard local practices.
Gabapentin dosage may be gradually increased based on individual patient response and tolerability, and as per standard practice in accordance with the drug label. The dose can be further increased in 300 mg/day increments (dose increments of 50% - 100%) every two to three days, up to a maximum dose of 3600 mg/day. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of two weeks, and to reach 3600 mg/day is a total of three weeks.
干预措施: Gabapentin (Drug)
Control group
Patients randomised to the control group will receive a prescription for a matching placebo. The starting dose will be the same as in the experimental group (100 mg three times a day per orally), additional to the analgesics according to standard local practices. Placebo can optionally follow the same dose scheme as described in the experimental arm.
干预措施: Placebo (Other)
结局指标
主要结局
Requirement of patients included in 7-week curative radio(chemo)therapy for a (dose-escalation of) strong opioid
时间窗: Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy)
Through pain diary, weekly visit by doctor and research assistant, the need for (dose-escalation of) strong opioid will be assessed.
次要结局
- Pain prevalence, prevalence of opioid use within HNCA patients(Daily, weekly and assessed at visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Maintenance or amelioration of pain within subtypes measured by the 0-10 numeric visual analogue pain rating scale.(Daily, weekly and assessed at visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Effect on percutaneous endoscopic gastrostomy tube placement(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Difference in dose of opioids needed for pain relief between the experimental and control group(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Effect on quality of life, and sleep quality in specific, of head and neck cancer patients assessed by EORTC QLQ C30(Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Effect on quality of life, and sleep quality in specific, of head and neck cancer patients assessed by HN35 Questionnaires(Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Effect on quality-adjusted life years(Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Drug tolerance(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Study drop-out(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Maintenance or amelioration of pain within subtypes measured by the Neuropathic Pain Scale(Daily, weekly and assessed at visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Maintenance or amelioration of pain within subtypes measured by the Brief Pain Inventory (Short Form).(Daily, weekly and assessed at visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up))
- Effect on treatment-related toxicity (mucositis, dysphagia, fatigue, weight loss)(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- (S)AE(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Acceptance rate of gabapentin(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Ease of use of trial medication(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Patient satisfaction(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))
- Selection of biomarkers to identify patients prone to develop HN cancer pain/treatment-related pain(At time of patient enrollment)
- Selection of biomarkers to select patients who benefit more from analgesic treatment with gabapentin(At time of patient enrollment)
- Effect on hospitalisation requirement(Continuous monitoring from patient enrollment until week 7 or date of requiring a (dose-escalation of) strong opioid if this occurs before week 7 (end of radio(chemo)therapy))