A Randomized Double-Blind Controlled Trial of Ketamine Versus Placebo in Conjunction With Best Pain Management in Neuropathic Pain in Cancer Patients
- To determine whether ketamine hydrochloride given in addition to best standard pain
management improves malignant neuropathic pain compared to best standard pain
management alone in patients with cancer.
- To compare initial treatment benefit (at day 4 of assessment period of 16 days) using
the sensory component of the McGill Short-Form Questionnaire.
- To compare difference in overall pain between the study arms based on the
pain-intensity visual-analogue score (VAS).
- To compare difference in neuropathic pain between the study arms based on the Leeds
Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale.
- To assess worst pain score (index neuropathic site) between the two arms.
- To compare patient distress between the two arms based on NCCN Distress Thermometer.
- To assess the side effects and tolerability of trial drug.
- To assess the effect of intervention on quality of life scores (based on Euroqol
thermometer), anxiety and depression (based on HADS), and opioid requirements.
OUTLINE: This is a multicenter study.
- Stage 1 (Run-in Period): Opioid doses are optimized, under a defined schedule, for up
to a maximum of 10 days to ensure that all patients are on an optimized and stable
regimen* prior to randomization. Following the run-in-period, patients undergo
reassessment. Patients who have improved pain scores (i.e., < 4/10 on the
visual-analogue score in the past 24 hours or < 5 McGill Sensory Scale Score) are taken
off the study. Patients whose scores have not improved continue on to Stage 2 of the
NOTE: *Stable regimen is defined as the same dose of controlled release and no more
variation than 2 breakthrough opioid doses over the normal for that patient for a period of
- Stage 2 (Titration Period): Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral ketamine hydrochloride 4 times a day. Doses are
titrated until when analgesia is achieved or individual side effects appear, for
up to 14 days.
- Arm II: Patients receive an oral placebo 4 times a day. Doses are titrated until
when analgesia is achieved or individual side effects appear, for up to 14 days.
- Stage 3 (Assessment Period): Patients receive the trial medication (i.e., ketamine
hydrochloride or placebo) at the fixed optimum dose (reached during the titration
period) for 16 days.
Patients are allowed to receive breakthrough opioids at any time during the study.
Patients complete quality-of-life and pain-assessment questionnaires periodically. Some
patients may undergo blood sample collection periodically for pharmacogenomics studies at a
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Time to treatment failure
Marie T. Fallon
Edinburgh Cancer Centre at Western General Hospital