Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery

Study Overview
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Brief Summary
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Breast cancer is the most common cancer in women in Europe. Therefore, breast cancer has become a chronic disease and patients need to learn to live with it as well as with the adverse effects related to the disease itself or to the therapies used. As noted in the third Plan cancer, pain is a major criterion in the quality of life of patients treated for breast cancer. Neuropathic pain was defined in 2011 by the international Association for the Study of Pain (I.A.S.P.) as the direct result of a lesion or disease affecting the somato-sensory system. Surgical treatment is often the first treatment of breast cancer. It can be conservative by performing a partial mastectomy (lumpectomy or quadrantectomy) or non-preservative by total mastectomy. Intercostobrachial neuralgia (NICB) or Post mastectomy painful Syndrome (MPRR) was first described by Wood in 1978 as chronic pain beginning immediately or early after a mastectomy Or a lumpectomy affecting the anterior thorax, armpit and/or arm in its upper half. These post-surgical pains are related to a lesion of the nerves in the breast area. In particular, the intercostobrachial nerve can be severed, stretched or crushed during surgery. Post-operative neuropathic pain in patients with breast cancer is underdiagnosed either by general practitioner or in a specialized environment. The diagnosis of neuropathic pain is performed during examination and clinical examination. Several scales allow to detect neuropathic pain but only the DN4 is recognized to be the most specific and sensitive scale. Patients do not always express this pain. They do not always reconcile with the surgery. Either because the pain occurs a long time after the surgery, or they find it normal to get hurt. These diagnostic difficulties cause a delay in setting up a suitable analgesic treatment. However, neuropathic pain responds poorly to common analgesics. Diagnosis, evaluation and early management of neuropathic pain are a priority in order to avoid their chronicization, to improve the quality of life of patients with breast cancer and to enable them to return to work quickly. We therefore assume that the diagnosis of early neuropathic pain at 2 months of surgery associated with initiation of appropriate topical treatment without the systemic effects of conventional oral treatments, would reduce the incidence of Chronic neuropathic pain 6 months after surgery.

Official Title
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Multicentric, Open, Randomized Study Comparing Topical Treatment by Patch of Capsaicin to 8% (Qutenza) to Pregabalin Oral in the Early Treatment of Neuropathic Pain After Primary Surgery for Breast Cancer

Conditions
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Breast Cancer Patient

Intervention / Treatment
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* Drug: Capsaicin
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female who had first breast cancer surgery, regardless of the type of surgery Age ≥ 18 years Healthy, non-irritated skin on painful areas to treat During the inclusion visit to M4 post surgery, neuropathic pain of the breast and / or axillary area corresponding to inter-brachial neuralgia with a DN4≥4 score. Obtaining the signed written consent of the patient Major patient affiliated to a social security scheme Exclusion Criteria: Contraindications specific to the treatments studied : capsaicine and pregabalin Diabetic patient Previous treatment with capsaicin or pregabalin Opioid treatment> 80 mg / day (oral morphine equivalent) in progress- Topical treatment of pain between surgery and inclusion visit Uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 90 mmHg) or recent history (<3 months) of cardiovascular events (stroke, heart attack, pulmonary embolism) Creatinine clearance (CLcr) <60mL / min according to the Cockcroft-Gault formula Pregnant woman, likely to be pregnant or breastfeeding Persons deprived of their liberty or guardianship (including curators), Impossibility of submitting to the medical follow-up of the test for geographical, social or psychological reasons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, open, randomized study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm CAPSAICINE topical<br>Application of capsaicin patches at 8% on the painful area 1 to 2 patches will be administered during the consultation. If necessary, a second application will be realized 3 months later. | Drug: Capsaicin<br>* Application of capsaicin patches at 8% on painful area<br>* Other names: qutenza EU/1/09/524/001;|
| Active Comparator: Arm PREGABALINE<br>Pregabalin tablets will be initiated at a dose of 50 mg / day taken in 2 doses Depending on the tolerance, the dose will be increased to 100 mg / day and then to 150 mg / day to reach a maximum dose of 600 mg / day. An interval of 3 to 7 days must be observed between each dose increase. | Drug: Pregabalin<br>* Taking Pregabalin tablets<br>* Other names: Lyrica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To show the noninferiority of early early medical treatment by topical treatment with capsaicin compared to oral treatment of pregabalin on the evolution of neuropathic pain after 2 months in patients who have undergone surgical excision of breast cancer | The 11-point numerical scale (0-10) is collected at 2 months. | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of an early medical treatment with capsaicin topical treatment compared to oral treatment pregabalin on the evolution of neuropathic pain in patients who had undergone excision surgical breast cancer after 6 months of treatment | The 11-point numerical scale of pain is also collected at the end of treatment | 6 months | 
| To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms: Questionnaire PGIC (patients' global impression of change) | Questionnaire PGIC is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms. | 6 months | 
| To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms | Questionnaire QLQ-C30 (quality of life questionnaire) is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms. | 6 months | 
| To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms | Questionnaire EQ-5D is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms. | 6 months | 
| Regression of the painful area after 2 and 6 months of treatment between the two arms. | The painful area is measured from pain mapping at baseline, and after 2 months and 6 months of treatment. It is measured by the area delimited by the contours of the painful surface (centralized reading). | 6 months | 
| Tolerance of each type of treatment by collecting side effects in each treatment arm. | The tolerance of the treatments will be measured by the number of patients having at least one adverse event of grade ≥ 2 according to the classification CTCAE v5.0. | 6 months | 
| Proportion of patients for whom only 1 application has been sufficient. | In the capsaicin arm, the number of total patches received by the patient during the 6 months will also be counted | 6 months | 
| Impact of peri-surgical anxiety and depression on the development of neuropathic pain after surgery for breast cancer | The HAD (Hospital anxiety and despression scale) questionnaire will be collected during the screening visit | 49 months | 
| The incidence of NICBs 4 months after surgery for breast cancer | The incidence of NICBs will be measured by the number of patients included in the study (DN4 +) compared to the number of patients screened before surgery | 4 months | 
| The evolution of the weight between the two arms after 6 months of treatment. | The weight is collected after 6 months of treatment | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer patient, Surgery, Inter Costobrachial Neuralgia