Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery (CAPTRANE)

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Patient
• Intervention / Treatment: Drug: Capsaicin; Drug: Pregabalin

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49000
    • Institut de Cancérologie de l'Ouest
  • Grenoble, France, 38700
    • CHU Grenoble
  • La Roche-sur-Yon, France, 85025
    • CHD Vendée
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lille, France, 59020
    • Hôpital Saint Vincent de Paul
  • Lyon, France, 69008
    • Centre Leon Berard
  • Nice, France, 06003
    • CHU Nice
  • Reims, France, 51100
    • Institut Jean Godinot
  • Saint-Cloud, France, 92210
    • Institut Curie
  • Toulouse, France, 31052
    • IUCT Oncopole
  • Valenciennes, France, 53322
    • CH Valenciennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm CAPSAICINE topical; 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; Application of capsaicin patches at 8% on painful area; Other Names: qutenza EU/1/09/524/001
Active Comparator: Arm PREGABALINE; 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; Taking Pregabalin tablets; Other Names: Lyrica

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Collaborators: Grünenthal GmbH
• Investigators: Study Director: DENIS DUPOIRON, MD, Institut de Cancérologie de l'Ouest

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): November 18, 2022
• Study Completion (Actual): November 18, 2022

Study Registration Dates

• First Submitted: November 5, 2018
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Breast cancer patient; Inter Costobrachial Neuralgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Breast Neoplasms; Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antipruritics; Pregabalin; Capsaicin
• Other Study ID Numbers: ICO-A-2018-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No