Tacrolimus as Treatment of Breast Cancer-Related Lymphedema

NCT ID: NCT04541290

Last Updated: 2022-02-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-22

Study Completion Date

2022-01-06

Brief Summary

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BACKGROUND Breast cancer-related lymphedema is a severe and life-long side-effect to breast cancer treatment. The condition increases the risk of infections and decreases health-related quality of life (HR-QOL) in patients. No prophylactic or curative treatment is currently available for this condition.

CD4+-cells plays a critical role in the development of lymphedema. The cells facilitate inflammation and fibrosis formation in the subcutaneous tissue which inhibits lymphatic regeneration. Tacrolimus is an immunosuppressive and anti-inflammatory macrolide that targets the CD4+-cells. Tacrolimus as treatment of lymphedema has already shown promising results in animal studies. Tacrolimus has the potential to cure an otherwise uncurable and life-long side-effect of BC and will therefore benefit a large number of patients who suffers from BCRL.

AIM To assess the effect of Tacrolimus treatment on breast cancer-related lymphedema METHOD Study design A pilot study with a planned inclusion of 20 patients with a 12 month follow-up period. The purpose of this study is to assess the effect of tacrolimus treatment on lymphedema and HR-QOL. Results are attained from objective measures and questionnaires.

The patients will be seen at a consultation prior to the treatment start and then 3 times hereafter (at 3, 6 and 12 months) as follow up consultations where effect of treatment is evaluated.

Primary endpoint:

\- Arm volume measured with water displacement test.

Secondary endpoints:

* Arm volume measured with measuring tape and calculated with volume of a cone formula
* Patient-reported outcome measured through the Danish versions of , LYMPH-ICF, DASH and SF-36 questionnaires
* Bioimpedance
* Lymphangiography Primary- and secondary endpoint data will be collected at each of the 3 consultations (prior to treatment and 3 and 6 months after the treatment start).

CLINICAL IMPACT This will be the first clinical pharmacological study on regarding treatment of lymphedema with Tacrolimus. This study will test the feasibility and efficacy of Tacrolimus ointment in a population of breast cancer patients who have developed lymphedema. The study may lead to a routine clinical implementation of tacrolimus ointment to patients diagnosed with Lymphedema. Regardless of the outcome, the study will benefit the patients and future research in the field of lymphedema.

Detailed Description

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Conditions

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Breast Cancer Lymphedema

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment

Women with stage 1-2 lymphedema due to breast cancer treatment

Group Type EXPERIMENTAL

Protopic 0.1 % Topical Ointment

Intervention Type DRUG

Applied in a thin layer covering all of the arm including the armpit and hand once a day for six months

Interventions

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Protopic 0.1 % Topical Ointment

Applied in a thin layer covering all of the arm including the armpit and hand once a day for six months

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age between 30-65 years
* Female
* Lymphedema diagnosis as a result of breast cancer treatment
* Active Lymphedema (excessive fluid)
* Significant lymphedema
* Grade I-II lymphedema
* Postmenopausal (Absence/lack of menstruation in at least 12 consecutive months) or continuously usage of contraceptive drugs (Spiral, birth-control pills, implant, transdermal patches, vaginal ring or depot injection). Contraceptive drugs must be used throughout the project and at least three weeks subsequent to the ending of the project (last application of the ointment).
* Clinically good general condition No lymphedema in the opposite arm (normal arm)
* Understands the purpose og the study and gives written consent to participate
* Can read and understand the danish language

Exclusion Criteria

* Pregnant, breast-feeding or with wish of pregnancy within the next year
* Bilateral breast cancer
* Grade 0, III or IV lymphedema
* Known allergies for Tacrolimus or and other macrolide
* Removal of lymph nodes in the opposite armpit
* Suffers from psychiatric disorders that may affect the participation in the project
* Reduced kidney or liver function
* Defect skin-barrier
* Diagnosed immunodeficiency
Minimum Eligible Age

30 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Odense University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Mads Gustaf Jørgensen

Doctor of Medicine, Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jens A Sørensen, MD Prof. PhD

Role: STUDY_CHAIR

Department of Plastic Surgery at Odense University Hospital

Locations

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Department of Plastic Surgery, Odense University Hospital

Odense, , Denmark

Site Status

Countries

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Denmark

References

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Zou L, Liu FH, Shen PP, Hu Y, Liu XQ, Xu YY, Pen QL, Wang B, Zhu YQ, Tian Y. The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: a 2-year follow-up prospective cohort study. Breast Cancer. 2018 May;25(3):309-314. doi: 10.1007/s12282-018-0830-3. Epub 2018 Feb 3.

Reference Type BACKGROUND
PMID: 29397555 (View on PubMed)

Ribeiro Pereira ACP, Koifman RJ, Bergmann A. Incidence and risk factors of lymphedema after breast cancer treatment: 10 years of follow-up. Breast. 2017 Dec;36:67-73. doi: 10.1016/j.breast.2017.09.006. Epub 2017 Oct 6.

Reference Type BACKGROUND
PMID: 28992556 (View on PubMed)

Grada AA, Phillips TJ. Lymphedema: Pathophysiology and clinical manifestations. J Am Acad Dermatol. 2017 Dec;77(6):1009-1020. doi: 10.1016/j.jaad.2017.03.022.

Reference Type BACKGROUND
PMID: 29132848 (View on PubMed)

Taghian NR, Miller CL, Jammallo LS, O'Toole J, Skolny MN. Lymphedema following breast cancer treatment and impact on quality of life: a review. Crit Rev Oncol Hematol. 2014 Dec;92(3):227-34. doi: 10.1016/j.critrevonc.2014.06.004. Epub 2014 Jul 2.

Reference Type BACKGROUND
PMID: 25085806 (View on PubMed)

Pusic AL, Cemal Y, Albornoz C, Klassen A, Cano S, Sulimanoff I, Hernandez M, Massey M, Cordeiro P, Morrow M, Mehrara B. Quality of life among breast cancer patients with lymphedema: a systematic review of patient-reported outcome instruments and outcomes. J Cancer Surviv. 2013 Mar;7(1):83-92. doi: 10.1007/s11764-012-0247-5. Epub 2012 Dec 5.

Reference Type BACKGROUND
PMID: 23212603 (View on PubMed)

Terada M, Yoshimura A, Sawaki M, Hattori M, Naomi G, Kotani H, Adachi Y, Iwase M, Kataoka A, Sugino K, Mori M, Horisawa N, Ozaki Y, Iwata H. Patient-reported outcomes and objective assessments with arm measurement and bioimpedance analysis for lymphedema among breast cancer survivors. Breast Cancer Res Treat. 2020 Jan;179(1):91-100. doi: 10.1007/s10549-019-05443-1. Epub 2019 Sep 18.

Reference Type BACKGROUND
PMID: 31535321 (View on PubMed)

Sackey H, Johansson H, Sandelin K, Liljegren G, MacLean G, Frisell J, Brandberg Y. Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery. Eur J Surg Oncol. 2015 Apr;41(4):577-84. doi: 10.1016/j.ejso.2014.12.006. Epub 2015 Jan 13.

Reference Type BACKGROUND
PMID: 25659877 (View on PubMed)

Ghanta S, Cuzzone DA, Torrisi JS, Albano NJ, Joseph WJ, Savetsky IL, Gardenier JC, Chang D, Zampell JC, Mehrara BJ. Regulation of inflammation and fibrosis by macrophages in lymphedema. Am J Physiol Heart Circ Physiol. 2015 May 1;308(9):H1065-77. doi: 10.1152/ajpheart.00598.2014. Epub 2015 Feb 27.

Reference Type BACKGROUND
PMID: 25724493 (View on PubMed)

Ogata F, Fujiu K, Matsumoto S, Nakayama Y, Shibata M, Oike Y, Koshima I, Watabe T, Nagai R, Manabe I. Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema. J Invest Dermatol. 2016 Mar;136(3):706-714. doi: 10.1016/j.jid.2015.12.001. Epub 2015 Dec 10.

Reference Type BACKGROUND
PMID: 27015456 (View on PubMed)

Muller GG, Jose NK, de Castro RS, de Holanda EC. Long-term use of topical tacrolimus ointment: a safe and effective option for the treatment of vernal keratoconjunctivitis. Arq Bras Oftalmol. 2019 Mar-Apr;82(2):119-123. doi: 10.5935/0004-2749.20190026. Epub 2019 Jan 24.

Reference Type BACKGROUND
PMID: 30698232 (View on PubMed)

Remitz A, Harper J, Rustin M, Goldschmidt WF, Palatsi R, van der Valk PG, Sharpe G, Smith CH, Dobozy A, Turjanmaa K; European Tacrolimus Ointment Study Group. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. Acta Derm Venereol. 2007;87(1):54-61. doi: 10.2340/00015555-0167.

Reference Type BACKGROUND
PMID: 17225017 (View on PubMed)

Gardenier JC, Kataru RP, Hespe GE, Savetsky IL, Torrisi JS, Nores GD, Jowhar DK, Nitti MD, Schofield RC, Carlow DC, Mehrara BJ. Topical tacrolimus for the treatment of secondary lymphedema. Nat Commun. 2017 Feb 10;8:14345. doi: 10.1038/ncomms14345.

Reference Type BACKGROUND
PMID: 28186091 (View on PubMed)

Harvey LA. REDCap: web-based software for all types of data storage and collection. Spinal Cord. 2018 Jul;56(7):625. doi: 10.1038/s41393-018-0169-9. No abstract available.

Reference Type BACKGROUND
PMID: 29977003 (View on PubMed)

Lasinski BB, McKillip Thrift K, Squire D, Austin MK, Smith KM, Wanchai A, Green JM, Stewart BR, Cormier JN, Armer JM. A systematic review of the evidence for complete decongestive therapy in the treatment of lymphedema from 2004 to 2011. PM R. 2012 Aug;4(8):580-601. doi: 10.1016/j.pmrj.2012.05.003.

Reference Type BACKGROUND
PMID: 22920313 (View on PubMed)

Damstra RJ, Glazenburg EJ, Hop WC. Validation of the inverse water volumetry method: A new gold standard for arm volume measurements. Breast Cancer Res Treat. 2006 Oct;99(3):267-73. doi: 10.1007/s10549-006-9213-0. Epub 2006 Jun 3.

Reference Type BACKGROUND
PMID: 16752072 (View on PubMed)

Pusic AL, Klassen AF, Scott AM, Klok JA, Cordeiro PG, Cano SJ. Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. Plast Reconstr Surg. 2009 Aug;124(2):345-353. doi: 10.1097/PRS.0b013e3181aee807.

Reference Type BACKGROUND
PMID: 19644246 (View on PubMed)

Wild D, Grove A, Martin M, Eremenco S, McElroy S, Verjee-Lorenz A, Erikson P; ISPOR Task Force for Translation and Cultural Adaptation. Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: report of the ISPOR Task Force for Translation and Cultural Adaptation. Value Health. 2005 Mar-Apr;8(2):94-104. doi: 10.1111/j.1524-4733.2005.04054.x.

Reference Type BACKGROUND
PMID: 15804318 (View on PubMed)

Klassen AF, Dominici L, Fuzesi S, Cano SJ, Atisha D, Locklear T, Gregorowitsch ML, Tsangaris E, Morrow M, King T, Pusic AL. Development and Validation of the BREAST-Q Breast-Conserving Therapy Module. Ann Surg Oncol. 2020 Jul;27(7):2238-2247. doi: 10.1245/s10434-019-08195-w. Epub 2020 Jan 21.

Reference Type BACKGROUND
PMID: 31965369 (View on PubMed)

Yamamoto T, Yamamoto N, Doi K, Oshima A, Yoshimatsu H, Todokoro T, Ogata F, Mihara M, Narushima M, Iida T, Koshima I. Indocyanine green-enhanced lymphography for upper extremity lymphedema: a novel severity staging system using dermal backflow patterns. Plast Reconstr Surg. 2011 Oct;128(4):941-947. doi: 10.1097/PRS.0b013e3182268cd9.

Reference Type BACKGROUND
PMID: 21681123 (View on PubMed)

Gulmark Hansen FC, Jorgensen MG, Sorensen JA. Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial. J Breast Cancer. 2023 Feb;26(1):46-59. doi: 10.4048/jbc.2023.26.e2. Epub 2023 Jan 19.

Reference Type DERIVED
PMID: 36762782 (View on PubMed)

Related Links

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http://www-dep.iarc.fr/NORDCAN/english/frame.asp

NORDICAN. Association of the Nordic Cancer Registries. Danish Cancer Society. Available from http://www.ancr.nu, accessed on 24 February 2020. Cancer \[Internet\]. 2011;1-2.

http://www.medlineplus.gov/druginfo/meds/a602020.html

Tacrolimus Topical: MedlinePlus Drug Information \[Internet\]. \[cited 2020 Feb 24\].

Other Identifiers

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Tacrolimus_2020

Identifier Type: -

Identifier Source: org_study_id

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