Study of Efficacy and Safety of Gabapentin to Reduce the Need for Strong Opioid Use in Head and Neck Cancer Patients. (stREnGTH)

Ghent University Hospital (UZ)

Status and phase: Withdrawn; Phase 3

Conditions: Head Neck Cancer; Pain, Neuropathic; Radiation Neuropathy

Treatments: Other: Placebo; Drug: Gabapentin

Study type: Interventional

Funder types: Other

Identifiers

NCT03747562

BC-2657

Details and patient eligibility

About

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).

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Experimental group

Experimental group

Description:

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.

Treatment:

Drug: Gabapentin

Control group

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo