The LYMPH Trial - Surgical Versus Conservative Complex Physical Decongestion Therapy for Chronic Breast Cancer-Related Lymphedema

Lymphedema, Breast Cancer Clinical Trial

— LYMPH  

Official title:

The LYMPH Trial - Surgical Versus Conservative Complex Physical Decongestion Therapy for Chronic Breast Cancer-Related Lymphedema: A Pragmatic, Randomized, Multicenter Superiority Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05890677
• Other study ID #: 2023-00733; mu21kappos
• Status: Recruiting
• Phase: N/A
• Start date: July 14, 2023
• Est. completion date: December 2035

Study information

• Verified date: March 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Elisabeth Kappos, PD Dr. med.
• Phone: +41 61 328 62 54
• Email: elisabeth.kappos[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to test whether lymphatic surgery provides better QoL (assessed with the Lymph-ICF-UL, (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema)) 15 months after randomization (and therefore about one year after surgery) compared to conservative treatment only for patients with chronic lymphedema (LE)

Description:

To date, conservative complex physical decongestion therapy (CDT) is the gold standard for BCRL (breast cancer related lymphedema) and includes manual lymphatic drainage, local compression with bandages and garments, physical exercises and meticulous skin care. It is, however, too often ineffective to prevent stage progression in curing BCRL and purely symptomatic. Lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are two surgical techniques that, in contrast to CDT, are able to actually address the underlying causes and eventually restore the lymphatic drainage. LVA achieves this by creating numerous bypasses between lymphatic vessels and venules allowing the drainage of excessive fluid within the subcutaneous tissues into the venous system, while VLNT usually brings functioning lymph nodes to an area devoid of lymph nodes or with dysfunctional lymph nodes, thus enabling the spontaneous development of new lymphatic pathways. Both techniques have shown very promising results with low complication rates and improved Quality of Life (QoL) for the patients. However, no multicentric randomized controlled trial (RCT) has yet prospectively evaluated the superiority of these surgical techniques over CDT alone, limiting patient's access to most effective treatment available. Requests for cost reimbursement must still be submitted to insurance companies in most countries and are often rejected, thus delaying surgical treatment and resulting in prolonged suffering of affected patients. This is untenable seeing as affected patients suffer from a heavy physical, psychological and financial burden. This pragmatic, randomized, multicenter trial aims to establish a solid scientific basis assessing the superiority of surgical treatment over CDT alone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: December 2035
• Est. primary completion date: June 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent.
• Patients = 18 years of age with prior treatment of breast cancer.
• At least one of the following prior breast cancer treatments: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), radiotherapy (RT) of chest wall or axilla or breast cancer surgery.
• Clinical diagnosis of chronic BCRL as defined by the ISL (inter-limb difference of >10% in volume or excess volume between the affected and non-affected limbs present for more than 3 months).
• Minimum of 3 months CDT.
• Ability to complete the QoL questionnaires.

Exclusion Criteria:

• No indication for lymphatic surgery according to clinical judgment of the treating surgeon (individual reasons will be specifically documented).
• Primary congenital LE or non-breast cancer-related LE.
• Need for immediate LE surgery according to clinical judgement by a specialist due to far progressed LE stage.

Related Conditions & MeSH terms

• Breast Cancer Lymphedema
• Breast Neoplasms
• Lymphedema
• Lymphedema, Breast Cancer

Intervention

Procedure:
• Surgical Intervention
LVA (Lymphovenous Anastomosis) and VLNT (Vascularised Lymph Node Transfer) are two advanced microsurgical techniques that are increasingly implemented in clinical practice in specialized centers and that are already carried out after health insurance application according to local standard of care. They have been studied in their respective mode of action as well as in their effectiveness in treating chronic BCRL (Breast Cancer-Related Lymphedema) in a multitude of mostly observational and single center studies with highly encouraging results. Patients in the interventional arm A will receive surgery with one of the two approaches or a combination of both, in a one or two-stage method, at the discretion of the treating surgeon. Depending on local standards one or both of the above might be combined with liposuction to the affected arm in a one or two-stage approach as well.
• Conservative Complex Physical Decongestion Therapy
Patients randomized to the control arm will receive CDT (Conservative Complex Physical Decongestion Therapy), which currently is considered as the best available standard of care. For this, patients will be referred to one of the dedicated LE (physical/skin) therapy clinics, if not already treated by one, according to their place of residence for continuation of standard conservative therapy. Recommendations to the procedures and treatment frequency of the conservative therapy will be made, but CDT will be done at the discretion of the treating physiotherapist.

Locations

Country	Name	City	State
Argentina	Universidad de Buenos Aires, Instituto de Oncología Ángel H. Roffo	Buenos Aires
Austria	Klinikum Klagenfurt	Klagenfurt
Belgium	University of Ghent	Gent
Brazil	Hospital Erasto Gaertner	Paraná	Curitiba
Canada	McGill University, Royal Victoria Hospital	Montreal
Canada	University of British Columbia, Gordon and Leslie Diamond Health Care Centre	Vancouver
Germany	Sana Kliniken Düsseldorf	Düsseldorf
Germany	Uniklinikum Erlangen	Erlangen
Germany	KEM Evang. Kliniken Essen-Mitte	Essen
Germany	BG Klinik Frankfurt am Main	Frankfurt
Germany	Universitätsklinikum Freiburg, Klinik für Plastische und Handchirurgie	Freiburg im Breisgau
Germany	Universitätsklinikum Göttingen	Göttingen
Germany	BG Klinik Ludwigshafen	Ludwigshafen am Rhein
Germany	Caritas Krankenhaus St. Josef/ Uniklinik Regensburg	Regensburg
Greece	Papageorgiou Hospital of Thessaloniki	Thessaloníki
Italy	Plastic and Reconstructive Surgery at Department of Surgical Science	Rome
Italy	Policlinic Gemelli, Operational Unit of Plastic Surgery	Rome
Netherlands	Maastricht University Medical Center	Maastricht
Romania	Institute of Oncology ''Prof. Dr. Ion Chiricu?a'' of Cluj-Napoca	Cluj-Napoca
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Sweden	Karolinska Institutet, K1 Molekylär medicin och kirurgi	Stockholm
Sweden	Department of Plastic and Reconstructive Surgery Uppsala University Hospital	Uppsala
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	University Hospital Basel	Basel
Switzerland	Hôpitaux Universitaires de Genève	Genève
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Ospedale Regionale di Lugano	Viganello	Lugano
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Klinik für Plastische, Rekonstruktive, Aesthetische und Handchirurgie	Zürich
United States	Harvard Medical School	Boston	Massachusetts
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Krebsforschung Schweiz, Bern, Switzerland, Rising Tide Foundation, Swiss National Science Foundation

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  Germany,  Greece,  Italy,  Netherlands,  Romania,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Quality of Life Questionnaire (Lymph-ICF-UL)	One of the most widely used PRO (patient reported outcome) instruments in chronic BCRL (breast cancer related lymphedema) is the LYMPH-ICF-UL-Questionnaire (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema), a rigorously developed and validated PRO instrument specific to BCRL. This questionnaire assesses the impairments in function, activity limitations and participation restrictions of patients with upper LE (limb lymphedema). It is a validated questionnaire, consisting of 29 items (questions) across five different domains. Each item is scored on a VAS (visual analog scale) ranging from 0 to 10. The total score on the LYMPH-ICF is equal to the sum of the item scores divided by the total number of answered items. A higher score on the Lymph-ICF indicates a greater impact on the functioning in daily life related to upper limb LE.	two time assessment at baseline and 15 month after randomization
Secondary	Change in Quality of Life Questionnaire (Lymph-ICF-UL)	One of the most widely used PRO (patient reported outcome) instruments in chronic BCRL (breast cancer related lymphedema) is the LYMPH-ICF-UL-Questionnaire (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema), a rigorously developed and validated PRO instrument specific to BCRL. This questionnaire assesses the impairments in function, activity limitations and participation restrictions of patients with upper LE (limb lymphedema). It is a validated questionnaire, consisting of 29 items (questions) across five different domains. Each item is scored on a VAS (visual analog scale) ranging from 0 to 10. The total score on the LYMPH-ICF is equal to the sum of the item scores divided by the total number of answered items. A higher score on the Lymph-ICF indicates a greater impact on the functioning in daily life related to upper limb LE.	13 time assessment up to 10 years after randomization
Secondary	Change in Quality of Life Questionnaire (LYMPH-Q)	The Lymph-Q Upper Extremity Module is a new PROM (patient-reported outcome measure) developed to assess patient reported outcomes of BCRL in a concept-driven approach. The complete questionnaire contains 68 questions covering the patient-relevant topics Health-related quality of life (arm appearance, arm function, arm symptoms, psychological), experience of care (information), and treatment (arm sleeve).	15 time assessment up to 10 years after randomization
Secondary	Change in Quality of Life Questionnaire (EuroQol EQ-5D-5L)	The 5-level EQ-5D version (EQ-5D-5L) consists of the EQ-5D descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions (5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems) resulting in a 1-digit number that expresses the level for that dimension. The digits for each dimension can be combined into a 5-digit number that describes the patient's health state.	15 time assessment up to 10 years after randomization
Secondary	Change in Pain score (visual analog scale)	The pain score consists of a VAS (visual analog scale) ranging from 0 (i.e. no pain) to 10 (i.e. worst pain). The VAS was published by the Yale University	7 time assessment up to 1 year