Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Headache

Pain

Head and Neck Neoplasms

Neuralgia

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neurologic Manifestations

Analgesics

All Drugs and Chemicals

Central Nervous System Depressants

Anticonvulsants

Psychotropic Drugs

Analgesics, Opioid

Gabapentin

Anti-Anxiety Agents

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

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.

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.

Gabapentin will be administrated orally, with or without food, and should be swallowed with sufficient fluid intake (e.g. a glass of water). Since head and neck cancer patients frequently experience swallowing difficulties, gabapentin capsules will be provided to enable opening of the capsule and use of the contents for mixture with food or liquids. Moreover, gabapentin powder can be dissolved in water to enable injection of the drug into a percutaneous endoscopic gastrostomy tube.

Placebo will be administrated orally, with or without food, and should be swallowed with sufficient fluid intake (e.g. a glass of water). Since head and neck cancer patients frequently experience swallowing difficulties, placebo capsules will be provided to enable opening of the capsule and use of the contents for mixture with food or liquids. Moreover, placebo powder can be dissolved in water to enable injection of the drug into a percutaneous endoscopic gastrostomy tube.

Placebo

Tom Boterberg, MD, PhD

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).

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.

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).

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.

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

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.

Through pain diary, weekly visit by doctor and research assistant, the need for (dose-escalation of) strong opioid will be assessed.

Through pain diary, weekly visit by doctor and research assistant, patients will be asked to rate their pain

Pain assessment of subtypes of patients, according to their tumour location, through the 0-10 numeric visual analogue pain rating scale. This scale is a tool to measure the pain of patients, with a score of 0 if the patient has no pain, a score of 5 if the patient has moderate pain and a score of 10 if the patient copes with the worst possible pain. So higher values represent worse pain.

Pain assessment of subtypes of patients, according to their tumour location, through the Neuropathic Pain Scale. Patients give a score between 0 until 10 on different aspects of pain as pain sharpness, heat/cold, dullness, intensity, unpleasantness, and surface vs. deep pain which all represent the subtypes of the Neuropathic Pain Scale. A score between 0 and 10 will be assigned to these different subtypes of pain, with a score of 0 if the patient has no pain, a score of 5 if the patient has moderate pain and a score of 10 if the patient copes with the worst possible pain. So higher values represent worse pain. The scores on all these subscales are not combined as we are interested in the subtypes of pain themselves.

Pain assessment of subtypes of patients, according to their tumour location, through the Brief Pain Inventory (Short Form).

Treatment-related toxicities will be scored by the local physician

Effect on hospitalisation will be assessed by the local physician and the research assistant

Effect on the placement of percutaneous endoscopic gastrostomy tube will be assessed by the local physician and research assistant

Monitoring of opioid therapy until primary endpoint

Monitoring of drug tolerance by local physician on weekly visits. The effects of the drug can either be unchanged, lessened, or increased. According to this, the physician will adapt the dose for patient. This will be weekly reported by the local physician to the research associate.

Monitoring of drug safety by local physician according to treatment-related toxicities, scored weekly by the local physicians according to the Common Terminology Criteria of Adverse Events (NCI CTCAE 5.0). Analgesic-induced side effects will be evaluated with regard to nausea, constipation, sleepiness, dizziness, confusion, hypersensitivities, urinary retention, pruritus and respiratory depression.

Weekly monitoring of drug compliance by local physician and research associate. Research associate counts amount of medication (gelules) that are left to assure there is therapy compliance.

Through pain diary, weekly visit by research assistant, patients will be asked about the ease of use of trial medication

Continuous follow-up of patients (weekly or daily) by research assistant

Through weekly visit by research assistant, patients will be asked how satisfied they are with current trial medication

Patients will be able to agree or disagree with the collection of blood samples on the informed consent form as these translational aspects are not an obligatory part of this trial. In patients who give their consent, one SST blood sample and one EDTA blood sample will be collected at the time of inclusion.

Spots Global Cancer Trial Database for radiation neuropathy