Novel Treatment Option for Neuropathic Pain (NoTOPain)

Sorlandet Hospital HF

Status and phase: Completed; Phase 2

Conditions: Complex Regional Pain Syndromes; Neuralgia

Treatments: Drug: Cetuximab; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02490436

2015-001195-21 (EudraCT Number)

SFK3 / 062202_281

2015/618/REK sør-øst D (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine whether the EGFR-inhibitor cetuximab is better than placebo for the treatment of neuropathic pain.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent and anticipated compliance.
• Pain defined as "definite" neuropathic pain, according to the Special Interest Group on Neuropathic Pain guidelines or defined as "probable" NP, according to the guidelines, if the confirmatory test was a positive diagnostic test. Complex regional pain syndrome can be included despite lack of an offending lesion, as long as the "Budapest criteria" are fulfilled
• Neuropathic Pain associated with compressive nerve states (including failed surgery) or CRPS (according to the "Budapest criteria")
• PainDETECT score of at least 13 with average pain intensity of at least 6 /10 over the last four weeks. In addition, a painDETECT pattern indicating that the underlying neuropathic pain is constantly present.
• Worst pain intensity higher than 6 for five of seven days during the screening phase, according to Brif Pain Inventory.
• The patient should be able to distinguish between the neuropathic pain and other pain conditions, including elements of nociceptive pain caused by the same disease process.
• Neuropathic pain duration of between six and thirty months, deemed chronic and likely to be irreversible by clinical history and findings.
• No new or increased neuropathic pain treatment for the last four weeks.
• Standard medical treatments for the patients' underlying condition or neuropathic pain must have been considered or tried and must, according to the opinion of the referring or a consulted pain specialist, be judged to be inappropriate or of insufficient potential efficacy.
• Referring physician agreement to follow up the patient after study completion according to the best possible and available pain treatment and care.
• Women of childbearing potential and men must use an acceptable method of contraception throughout the study, and for 30 days after the last study drug administration.
• Negative pregnancy test within 7 days before each treatment period where appropriate.
• White blood cell count ≥ 3 × 109 with neutrophils ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin ≥ 6.21 mmol/L (10 g/dL). Total bilirubin ≤ 1.5 × upper limit of reference range and AST and ALT ≤ 2.5 × upper limit of reference range within the last 28 days before inclusion.
• Aged 18 or above

Exclusion criteria

• Neuropathic pain origin in the central nervous system.
• Phantom limb pain or a significant component of nociceptive pain.
• Ascending distal small fiber peripheral neuropathy.
• Patients primarily experiencing pain 'attacks', i.e. pattern of neuropathic pain depicted in picture 3 of the painDETECT.
• Other pain state that may interfere with evaluation of the studied neuropathic pain condition.
• Any underlying medical or psychiatric condition, clinical disorder or laboratory finding, which in the opinion of the investigator may interfere with study objectives.
• Uncontrolled or unstable diabetes.
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias
• Severe cerebrovascular disease during the six months prior to inclusion.
• Active and ongoing eye and skin disorders or newly diagnosed gastric ulcer that may interfere with the study treatment.
• History of allergic reaction to any of the study treatment components, red meat or tick bites.
• Previous treatment with any EGFR-pathway inhibitor.
• Women who are pregnant or breastfeeding.
• Participation in another clinical trial within the past 90 days.
• Use of any investigational agent within 90 days prior to day 1 of study drug.
• Known drug abuse/alcohol abuse, legal incapacity or limited legal capacity or any other reason that, in the opinion of the investigator precludes the subject from participating.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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15 participants in 2 patient groups

A: active drug first

Experimental group

Description:

Cetuximab in treatment period 1, placebo in treatment period 2, and open-label cetuximab in treatment period 3.

Treatment:

Drug: Cetuximab

Drug: Placebo

B: placebo first

Experimental group

Description:

Placebo in treatment period 1, cetuximab in treatment period 2, and open-label cetuximab in treatment period 3.

Treatment:

Drug: Cetuximab

Drug: Placebo