Secondary Lymphedema
Conditions
Keywords
secondary lymphedema, breast cancer, dual mRNA therapy
Brief summary
Lymphedema is a common complication of breast cancer treatment, affecting approximately a quarter of patients. Those affected can have an uncomfortable, unsightly and sometimes functionally impaired limb prone to episodes of superficial infection. The aetiology and pathophysiology of lymphedema in patients with breast cancer appear to be multifactorial and are still not fully understood.Although conservative treatment techniques can be very successful in controlling symptoms, they do not afford a cure. In this situation of unmet medical need, it is essential to find a new therapeutic solution to treat lymphedema. The approach of the LYMPHARN project is based on dual mRNA strategy delivered by FlashRNA® vector targeting both lymphatic endothelium and surrounding adipose tissue function.
Interventions
DRUGAPERNAVEC
At day 0, the injection of APERNAVEC vector will be performed in intradermic tissue of the limb affected by lymphedema. Patient will be follow-up for 6 months
Sponsors
University Hospital, Toulouse
Flash Therapeutics
RNAlead
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women who developed upper limb lymphedema after surgery for breast cancer hormone receptor positive (HR+) more than 5 years, * Age\> 18 years, * Body mass Index (BMI)\<40, * Stage 2 Lymphedema, moderate (defined by an increase in volume between 20 and 40% compare to the healthy limb), * Lymphedema evolving during at least 6 months, * Patient who adhere to optimized decongestive therapy, including a compression sleeve worn daily, integrated into an educational care pathway for the management of their lymphedema, * Patients information and signed written consent form, * Patients affiliated to a social security system.
Exclusion criteria
* HER2+ breast cancer triple positive, * Other aggressive breast cancers (including triple negative and inflammatory breast cancer), * Active cancer needing chemo- or radio-therapy, * Metastatic breast cancer, * Bilateral breast cancer, * Upper limb peripheral arterial disease ipsilateral to the lymphedema, * History of recent (\< 3 months) upper limb deep venous thrombosis ipsilateral to the lymphedema, * Previous shoulder or orthopedic surgery on lymphedematous arm * Any abnormality of the opposite arm (arm without lymphedema), * Trophic disorders on the lymphedematous arm, * Last episode of cellulitis less than six months, * Recurrent cellulitis, * Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months or within 5 half-lives of any investigational product Immunosuppressive and anti-inflammatory treatments (topical and anti-inflammatory dermocorticoids and oral corticosteroids) in the 10 days before the injection or within 5 half-lives. * Patient under judicial protection or enable to express consent, * Females who are or plan to be pregnant or breastfeeding during the course of this study, * Women of childbearing potential (WOCBP) who are sexually active and unwilling to use an adequate birth control method (hormonal or physical barrier), * History of cancer other than breast cancer (excepted basalcell carcinoma), * Any acute, chronic, or severe psychiatric condition that may interfere with participation in the study * Unstable, clinically significant neurologic, psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results. * Known allergy to bovine proteins * Vulnerable patients (persons deprived of their liberty by judicial or administrative decision, persons undergoing psychiatric treatment, persons admitted to a health or social establishment for purposes other than research) according to article L1121-6 of the Public Health Code.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile of APERNAVEC vector injection during the month following the injection | Day 1, Day 2, Day 5, Day 10 and 1 month after injection | To determine the safety profile with the number, the type and the severity of adverse events) occurring |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile of APERNAVEC vector injection during 6 months following the injection | 1 month, 3 months and 6 months after injection | Number, type and severity of adverse events occurring between M1 and M3 and between M3 and M6. |
| Feasibility of the procedures | Day 0 (injection visit) | Feasibility will be assessed through the number of patients for whom the injection is actually performed |
| local and systemic inflammatory reaction following injections | Day 0 (post injection), Day 1, Day 2, Day 10, 1 month, 3 months and 6 months after injection | Local and systemic inflammation and immune response following injection is a composite measure derived of 5 validated components: fever monitoring, change in the temperature of the treated limb (assessed with a thermal camera), levels of CRP, Fibrinogen, leukocyte ratios, lymphocyte subpopulations, level of Immunoglobulins panel, photographies ( to assess changes in the appearance of the treated limb) and volumetric variation of the affected limb. All of this components are essential and will be aggregated to arrive at one reported value : local and systemic inflammatory reaction following injections |
| Efficacy of injections | Day 1, Day 2, Day 10, 1 month, 3 months and 6 months after injection | Efficacy will be explored through a composite measure derived from volumetric reduction of the affected limb, change in thickness and stiffness of the cutaneous and subcutaneous tissue of the fore-arm and arm assessed by ultrasound, analysis of modification in the lymphedema capillary network assessed by lymphofluoroscopy, by lymphoscintigraphy, by lymphoMRI, and change in quality of life assessed by the Lymphcol Arm and the SF36 questionnaires. All of this components are essential and will be aggregated to arrive at one reported value : efficacy of injections |
| Pharmacokinetic of the APERNAVEC vector in the blood | Day 0, 4 hours post injection, 24h (Day 1), 48h (Day 2), Day 10 and1 month after injection | Pharmacokinetic of the APERNAVEC vector will be studied through dosage of the vector (p24 protein) in blood by ELISA |
| plasma biobanking | Day 0, Day 10 and 1 month after injection | Constitute a plasma biobanking with blood samples |
Countries
France
Contacts
CONTACTCharline DAGUZAN
PRINCIPAL_INVESTIGATORJulie MALLOIZEL-DELAUNAY, Dr
Hôpital Rangueil, CHU Toulouse
Outcome results
None listed