Lymphedema After Gyneco-oncologic Treatment

NCT ID: NCT05469945

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 218 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2028-06-30

Brief Summary

Trial developed to inventory the incidence of early and advanced stage lower limb lymphedema in patients diagnosed with and treated for gynaecologic cancer.

Four hundred patients with diagnosis stage 1-3 gynaecologic cancer will be included in an observational cohort between diagnosis until maximum 2 weeks after start of the first treatment. They will be followed for occurrence of lower limb lymphedema up till 2 years after their last treatment.

Data on signs and symptoms, quality of life, time investment and financial expenses will be collected, to provide information on the incidence and risk factors for lower limb lymphedema, and on its impact on patients, regarding quality of life, sexual well-being and time- and financial investment.

Patients developing early stage LLL enter an interventional sub-cohort, in which the effect of class II compressive garments on preventing evolution towards advanced stage LLL will be evaluated.

Detailed Description

Context of the problem: Improved knowledge on the diagnosis and treatment of cancer has resulted in an increased number of cancer survivors. Consequently, more patients are confronted, often life-long, with the complications of their cancer treatment. These chronic conditions impact daily functioning and quality of life (QoL), complicate the return to work and undermine psycho-social well-being. One of the most frequent and disabling complications is lymphedema, a condition undermining QoL to an extent exceeding even a 10-year age increase.

The damage of lymphedema covers many aspects of daily life: it changes body image and complicates daily activities as basic as clothing, it increases patient-related health expenditures for treatment and for coping with the disease, reduces patient autonomy in daily functioning and can even cause sensory or motor dysfunctions. So far, no definitive cure exists for lymphedema: patients are confined to life-long preventive measures, compression therapy and regular manual lymph drainage. Surgical repair may be an option in selected cases, but evidence on surgical techniques is limited and their long-term effects are still unknown. Moreover, even after successful repair, conservative treatment is still needed.

Most studies on lymphedema are limited to upper limb lymphedema (ULL), mainly after breast cancer treatment. Only a few publications focus on lower limb lymphedema (LLL), despite its detrimental impact on QoL. This could be due to the difficulties to diagnose and treat LLL in comparison to ULL: LLL often occurs bilaterally or at the level of the groins or genital region, hence impeding diagnosis through comparison. Perimetric measurement of large cone-like oedematous legs is cumbersome. Manual lymph drainage and application of compressive garments is more strenuous for legs than for arms, and the typical bilateral occurrence and large volumes of LLL inflate the cost of treatment garments. However limited, some groups did evaluate the incidence of LLL after pelvic treatment, but maintained the criteria for advanced stage lymphedema as cut off, thereby underestimating the prior phases in which patients are confronted with functional impairment due to LLL, without apparent swelling.

The observational cohort in this study is aimed at inventorying the incidence, timing and risk factors of early as well as advanced stage lymphedema. Time and cost-investment of patients for prevention and/or treatment of LLL will be analyzed. The impact of LLL on QoL and on sexual well-being will be calculated.

A sub-cohort of this trial is of interventional design: in patients, included in the observational cohort and developing early stage LLL, standard of care treatment will be started, including skin care, active exercises and manual lymph drainage. In the experimental group, compressive garments class II will be added and compliance as well as tolerance of these garments will be analyzed.

Side-kicks of this trial are the standardization of perimetric measurements of the legs, validation of a self-report LLL screening tool and testing of the sensitivity and specificity of ICG fluoroscopy to detect early stage LLL.

Sample size calculation:

The sample size is calculated for the interventional sub-cohort, to have at least 80% power to detect a difference between the compression group and the control group for progression of lymphedema. An alpha has been set equal to 0.05.

Sample size calculation is based on evaluation at year 1. No longitudinal analysis is foreseen as primary analysis, but this could be included as a secondary analysis using a GEE analysis.

To detect a difference, in the interventional sub-cohort 109 subjects are required per group (2*109=218 subjects in total for the two groups) to have at least 80% power. If 66% of the patients in the observational cohort will meet the inclusion criteria for the interventional randomized trial, at least 330 (=218/0.66) patients should be included in the observational cohort. To correct for drop out we planned to include 400 patients. This number is feasible within the planned recruitment period of 18-24 months. If the number of subjects would be reached before the end of the planned recruitment period, recruitment will be stopped at 400 patients. If the number is not attained, the recruitment period will be prolonged. If the number of 218 subjects is reached in the interventional sub-cohort, randomization will be stopped and analysis starts. However, the observational cohort will continue accrual until 400 subjects are reached.

We assume a difference in true transition rates (T1 to T3) in both study arms, with 0.4 in the interventional group versus 0.75 in the control group. The recruitment of 109 patients in each treatment arm would allow the assessment of benefit of the intervention with 80% power, based on the 95% two-sided confidence interval approach for the differences in two independent proportions.

Conditions

Lymphedema; Genital Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control arm: no compressive garments

Patients detected with early stage LLL (0-1 ISL stadia) start with education and preventive measures.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventional arm: start of CC2 compressive garments

Patients in the experimental arm and detected with early stage LLL (0-1 ISL stadia) start with CC2 compressive garments in addition to education and preventive measures.

Group Type: EXPERIMENTAL

Compressive garments class II

Intervention Type: DEVICE

Daily wearing of compressive garments, especially during prolonged standing upright or strenuous activities.

Interventions

Compressive garments class II

Daily wearing of compressive garments, especially during prolonged standing upright or strenuous activities.

Intervention Type: DEVICE

Other Intervention Names

Flat knit Medi Cosy compression class II stockings and/or bermuda

Eligibility Criteria

Inclusion Criteria

• Signed informed consent (ICF)
• Female patient, recently diagnosed with gynaecologic cancer (cervix, endometrium, vulva, vagina, ovaries…) and candidate for curative treatment
• Age ≥ 18 years
• Understanding of the Dutch language
• Able to understand the informed consent and willing to comply with the protocol, including use of diary or app and timely completion of requested questionnaires.

Exclusion Criteria

• History of treatment for gynaecologic cancer
• Concurrent second primary tumor(s)
• Pregnancy or pregnancy planned within 2 years
• Known metastasized cancer at the time of inclusion (D0)
• Severe injury, surgery or deformation of the legs or groins in the past
• Vascular malformation of the leg or untreated venous insufficiency with oedema (CEAP C4 or more)
• Mental or psychological problems, inability to comply to the study protocol
• First treatment administered > 2 weeks before
• Clinical signs and symptoms of lymphedema present (ISL stage 0 or higher) at the moment of intake

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Louvain

UNKNOWN

Sponsor Role: collaborator

Kom Op Tegen Kanker

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Monten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital, Dept. Radiotherapy-Oncology

Ghent, , Belgium

Site Status: RECRUITING

University Hospital, Louvain

Leuven, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Chris Monten, MD, PhD

Role: CONTACT

chris.monten@uzgent.be

093320749

Caren Randon, MD, PhD

Role: CONTACT

caren.randon@uzgent.be

093326252

Facility Contacts

Chris Monten, M.D., PhD

Role: primary

chris.monten@uzgent.be

+32 9 332 0749

Caren Randon, M.D., PhD

Role: backup

caren.randon@uzgent.be

+32 9 332 6252

Nele Devoogdt, PhD

Role: primary

nele.devoogdt@uzleuven.be

016342515

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Other Identifiers

BC 09915

Identifier Type: -

Identifier Source: org_study_id