The Role of Coadministration of Lidocaine and Ketamine in Opioid-Refractory Chronic Cancer-Related Pain.

NCT07408193 | Not Yet Recruiting Early Phase 1

• 1 other identifier: 801/30-12-2025
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blinded, placebo-controlled, cross-over trial examining the effect of a series of two weekly intravenous infusions of lidocaine 4 mg/kg and ketamine 0.2 mg/kg in patients with moderate to severe opioid-refractory chronic cancer-related pain. The aim of this study is to investigate whether the lidocaine - ketamine (LK) regimen provides better analgesia that an active placebo of midazolam 0.02 mg/kg, in this population.

Conditions

Opioid-Refractory Chronic Cancer-Related Pain

Keywords

Cancer Pain; Treatment-Resistant Chronic Pain; Lidocaine; Ketamine; Analgesics, Adjuvant; Infusions, Intravenous; Cross-Over Studies; Double-Blind Method; Patient Reported Outcome Measures; Opioid-Related Disorders; Neoplasms

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in the Worst Pain During the Last 24 Hours on an 11-Point, 0 to 10, Numerical Rating Scale

  Question 3 of the Brief Pain Inventory - Short Form, where 0 is equivalent to no pain and 10 indicates the worst possible pain.

  Baseline (immediately before the first LK or placebo infusion) and one week after the second infusion.

Secondary Outcomes (7)

• Changes in the Score of Pain Intensity of the Brief Pain Inventory - Short Form

  Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).

• Change in the Proportion of Patients Achieving 2-Point Reduction on Worst and Least Pain of the Brief Pain Inventory - Short Form

  Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).

• Change in the Score of the Interference Scale of the Brief Pain Inventory - Short Form

  Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).

• Change in total Oral Morphine Equivalents Consumption of the Previous Week

  Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).

• Immediate Analgesic Effect of the Infusion (LK or placebo)

  Before the infusion and one hour after infusion termination.

Study Arms (2)

Lidocaine and Ketamine Infusion

ACTIVE COMPARATOR

Drug: Lidocaine and Ketamine Infusion

Active Placebo (Midazolam) Infusion

PLACEBO COMPARATOR

Drug: Active Placebo (Midazolam) Infusion

Interventions

Lidocaine and Ketamine Infusion DRUG

Participants receive two intravenous infusions, 7 days apart, containing lidocaine 4 mg/kg and ketamine 0.2 mg/kg (using actual body weight, or ideal body weight if BMI \>30). The drugs are combined in a single, clear solution and administered via an electronic pump in an outpatient setting.

Lidocaine and Ketamine Infusion

Active Placebo (Midazolam) Infusion DRUG

Participants receive two intravenous infusions, 7 days apart, containing midazolam 0.02mg/kg (using actual body weight, or ideal body weight if BMI \>30). The drugs are combined in a single, clear solution and administered via an electronic pump in an outpatient setting.

Active Placebo (Midazolam) Infusion

Eligibility Criteria

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

You may qualify if:

• Age 18 years or more
• Capacity to provide informed consent, ability to complete study assessments and comply with the study procedures
• Meets the IASP definition for chronic cancer-related pain
• Moderate or severe pain, defined as average pain of 4 or greater on an 11-point (0-10) NRS in the past 24h
• Adequate trial of opioid medication, defined as a dose of at least 60 mg/day oral morphine equivalent or maximum tolerated dose, in the past 24h
• For patients with neuropathic component to pain: adequate trial of at least one adjuvant analgesic, defined as a daily dose of at least Amitriptyline 37.5mg, Duloxetine 30mg, Gabapentin 900mg, Pregabalin 150mg, Venlafaxine 60mg or equivalent (26), or maximum tolerated dose in the past 24h

You may not qualify if:

• Previous adverse reaction to ketamine, lidocaine or other amide-type local anesthetics, midazolam
• Severe liver disease (Child Class B or C)
• SGPT or SGOT \>5 times the upper limit of normal
• End stage kidney disease
• Serious cardiac comorbidity (e.g. unstable angina, poorly controlled hypertension or tachycardia, high-risk coronary vascular disease, symptomatic heart failure with NYHA class III-IV, history of heart block, Wolf-Parkinson-White syndrome, Adams-Stokes syndrome)
• Elevated intracranial or intraocular pressure
• Pheochromocytoma or poorly controlled hyperthyroidism
• History of psychosis, schizophrenia or substance abuse
• Pregnant or breastfeeding
• Porphyria
• Life expectancy shorter than the duration of the study

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead
• Attikon Hospital: collaborator

Study Sites (1)

University General Hospital of Athens "Attikon" - National and Kapodistrian University of Athens Medical School

Athens, Attica, 12461, Greece

Location

Related Publications (24)

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• WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK537492/

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Related Links

• Related Info

MeSH Terms

Conditions

Cancer Pain; Opioid-Related Disorders; Neoplasms

Interventions

Lidocaine; Midazolam

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Konstantinos Kalimeris, Assoc Prof of Anesthesiology

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Maria Riga, Assis Prof of Anesthesiology

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Ioannis Kotsantis, Assis Prof of Oncology

  National and Kapodistrian University of Athens

  STUDY CHAIR

Central Study Contacts

Konstantinos Kalimeris MD, PhD, Associate Professor of Anesthesiology, Associate Professor

CONTACT

+302105831997; kkalimeris@med.uoa.gr

Erond Zeneli MD, PhD candidate

CONTACT

+306982094129; erond.zeneli@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 13, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: They will be available from the end of the recording of the response of the last patient and for 5 years thereafter.
• Access Criteria: Researchers that would have come in contact with our team firstly and that shall be able to prove that they will use the data solely for research purposes and not for commercial use.

Locations

GR (1)