Topical tacrolimus for the amelioration of breast cancer-related lymphedema: a randomized, double-blind, placebo-controlled phase II/III trial

2023-503644-13-00 Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 9 Sep 2024 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 3 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 80
Countries 1
Sites 3

Breast cancer-related lymphedema

The objective of this trial is to evaluate and confirm the previously observed effect of topical tacrolimus on stage I and II breast cancer-related lymphedema (BCRL). Specifically, we aim to compare the impact of tacrolimus ointment to a placebo ointment on various parameters including lymphedema volume, health-related…

Key facts

Sponsor
Odense University Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Female
Therapeutic area
Diseases [C] - Hemic and Lymphatic Diseases [C15]
Trial duration
9 Sep 2024 → ongoing
Decision date (initial)
2024-05-16
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The objective of this trial is to evaluate and confirm the previously observed effect of topical tacrolimus on stage I and II breast cancer-related lymphedema (BCRL). Specifically, we aim to compare the impact of tacrolimus ointment to a placebo ointment on various parameters including lymphedema volume, health-related quality of life (HRQoL), lymphatic flow and function, skin fibrosis, and excess water accumulation in the affected limb. The primary endpoint, assessed at the 12-month follow-up, focuses on achieving a minimum of 10% reduction in lymphedema volume. We hypothesize that this volume reduction will lead to a significant improvement in both subjective and objective symptoms associated with lymphedema. Additionally, we anticipate that patients may experience a reduction in the need for other concomitant lymphedema treatment modalities.

Conditions and MedDRA coding

Breast cancer-related lymphedema

VersionLevelCodeTermSystem organ class
20.0 LLT 10025233 Lymphedema 10047065

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Age > 18 years
  2. BCRL ISL stage I or II
  3. Pitting edema
  4. Postmenopausal or use of Contraceptive drugs
  5. Healthy opposite arm
  6. L-Dex score>10
  7. Lymphedema volume >10% of healthy arm
  8. Comprehension of Danish
  9. Female

Exclusion criteria 9

  1. Pregnant, breast-feeding, or aiming to conceive within the next year
  2. Bilateral breast cancer
  3. Contralateral lymphadenectomy
  4. Allergy to tacrolimus, macrolides, or iodine
  5. Pacemaker implant
  6. Known kidney or liver disease
  7. Defect skin-barrier on the affected arm
  8. Diagnosed immunodeficiency or treated with immunosuppressive medicine
  9. No previous surgical treatment for lymphedema

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Change in lymphedema volume

Secondary endpoints 4

  1. Health-related quality of life
  2. Lymphatic flow and - function
  3. Skin fibrosis
  4. Excessive water in the limb (L-Dex score)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Tacrolimus

SUB10797MIG · Substance

Active substance
Tacrolimus
Pharmaceutical form
OINTMENT
Route of administration
CUTANEOUS USE
Max daily dose
3 g gram(s)
Max total dose
1200 g gram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo

SUB21402 · Substance

Active substance
Placebo
Pharmaceutical form
OINTMENT
Route of administration
CUTANEOUS USE
Max daily dose
1 g gram(s)
Max total dose
365 g gram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

51 Total trials 30 Recruiting 11 Ended
Academic / Non-commercial
Sponsor organisation
Odense University Hospital
Address
J B Winsloews Vej 4
City
Odense C
Postcode
5000
Country
Denmark

Scientific contact point

Organisation
Odense University Hospital
Contact name
Principal investigator

Public contact point

Organisation
Odense University Hospital
Contact name
Principal investigator

Third parties 2

OrganisationCity, countryDuties
Odense University Hospital
ORG-100007716
 Odense C, Denmark On site monitoring, Code 10, Code 5, Data management, E-data capture, Code 8
Glostrup Apotek
ORG-100028772
 Glostrup, Denmark Code 14

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruitment ended 80 3
Rest of world — 0 —

Investigational sites

Denmark

3 sites · Ongoing, recruitment ended
Lillebaelt Hospital
Department of Plastic Surgery, Beriderbakken 4, 7100, Vejle
Zealand University Hospital
Department of Plastic and Breast Surgery, Sygehusvej 10, 4000, Roskilde
Odense University Hospital
Department of Plastic Surgery, J B Winsloews Vej 4, 5000, Odense C

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2024-09-09 2024-09-09 2025-09-29

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2023-503644-13-00 2.2
Protocol (for publication) D4_dash_danish 1
Protocol (for publication) D4_LYMPH_Q Upper Extremity Danish DK 1
Protocol (for publication) D4_SF-36 1
Recruitment arrangements (for publication) K1_Template_recruitment_arrangements 2.1
Recruitment arrangements (for publication) K2_Recruitment_material_Tacro 1.1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Adults 1.6
Subject information and informed consent form (for publication) L1_SIS_and_ICF_OLE 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Tacrolimus Accord 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-03-10 Denmark Acceptable
2024-05-08
 2024-05-16
2 SUBSTANTIAL MODIFICATION SM-1 2025-06-11 Denmark Acceptable
2025-08-29
 2025-08-29
3 NON SUBSTANTIAL MODIFICATION NSM-1 2026-03-10 Denmark Acceptable
2025-08-29
 2026-03-10