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

NCT03747562 | Withdrawn Phase 3 DMC

• 1 other identifier: BC-2657
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Head Neck Cancer; Radiation Neuropathy; Pain, Neuropathic

Keywords

Gabapentin

Outcome Measures

Primary Outcomes (1)

• Requirement of patients included in 7-week curative radio(chemo)therapy for a (dose-escalation of) strong opioid

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

  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 (19)

• 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)

• 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)

Study Arms (2)

Experimental group

EXPERIMENTAL

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.

Drug: Gabapentin

Control group

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Gabapentin DRUG

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.

Experimental group

Placebo OTHER

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.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 be 18 or older at the time of enrolment
• Patients should be able to adequately communicate in Dutch or French

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Ghent: lead
• General Hospital Groeninge: collaborator
• KU Leuven Campus Kulak Kortrijk: collaborator
• Anglia Ruskin University: collaborator

Study Sites (2)

UZ Ghent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

AZ Groeninge

Kortrijk, West-Vlaanderen, 8500, Belgium

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Neuralgia

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Tom Boterberg, MD, PhD

  Head of Clinic, Radiation Oncologist Department of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: November 20, 2018
• Study Start: March 1, 2019
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)