Clinical trial NCT03747562: Study of Efficacy and Safety of Gabapentin to Reduce the Need for Strong Opioid Use in Head and Neck Cancer Patients.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Head Neck Cancer
Radiation Neuropathy
Pain, Neuropathic
Keywords: Gabapentin
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: General Hospital Groeninge
name: KU Leuven Campus Kulak Kortrijk
name: Anglia Ruskin University
First posted: 2018-11-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised-controlled trial where patients are randomised to either the experimental group (E) receiving gabapentin or the control group (C) receiving a matching placebo, both in addition to standard analgesic therapy (WHO ladder steps 2 and 3).
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Requirement of patients included in 7-week curative radio(chemo)therapy for a (dose-escalation of) strong opioid
timeFrame: 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)
Secondary outcomes:
measure: Pain prevalence, prevalence of opioid use within HNCA patients
timeFrame: 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)
measure: Maintenance or amelioration of pain within subtypes measured by the 0-10 numeric visual analogue pain rating scale.
timeFrame: 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)
measure: Maintenance or amelioration of pain within subtypes measured by the Neuropathic Pain Scale
timeFrame: 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)
measure: Maintenance or amelioration of pain within subtypes measured by the Brief Pain Inventory (Short Form).
timeFrame: 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)
measure: Effect on treatment-related toxicity (mucositis, dysphagia, fatigue, weight loss)
timeFrame: 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)
measure: Effect on hospitalisation requirement
timeFrame: 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)
measure: Effect on percutaneous endoscopic gastrostomy tube placement
timeFrame: 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)
measure: Difference in dose of opioids needed for pain relief between the experimental and control group
timeFrame: 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)
measure: Effect on quality of life, and sleep quality in specific, of head and neck cancer patients assessed by EORTC QLQ C30
timeFrame: Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up)
measure: Effect on quality of life, and sleep quality in specific, of head and neck cancer patients assessed by HN35 Questionnaires
timeFrame: Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up)
measure: Effect on quality-adjusted life years
timeFrame: Visit 1 (moment of inclusion), visit 2 (anticipated week 5), visit 3 (end of radio(chemo)therapy), and week 24 (follow-up)
measure: Drug tolerance
timeFrame: 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)
measure: (S)AE
timeFrame: 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)
measure: Acceptance rate of gabapentin
timeFrame: 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)
measure: Ease of use of trial medication
timeFrame: 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)
measure: Study drop-out
timeFrame: 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)
measure: Patient satisfaction
timeFrame: 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)
measure: Selection of biomarkers to identify patients prone to develop HN cancer pain/treatment-related pain
timeFrame: At time of patient enrollment
measure: Selection of biomarkers to select patients who benefit more from analgesic treatment with gabapentin
timeFrame: At time of patient enrollment
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: UZ Ghent
state: Oost-Vlaanderen
city: Kortrijk
country: Belgium
facility: AZ Groeninge
state: West-Vlaanderen
Study officials:
affiliation: Head of Clinic, Radiation Oncologist Department of Radiation Oncology
name: Tom Boterberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: