Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer

NCT03838419 | Suspended

• 1 other identifier: COSMOPOLITAN
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is the most frequent malignancy in women. Standard therapy for early-stage breast cancer is breast conserving surgery (BCS) followed by adjuvant whole breast irradiation (WBI), which usually requires a treatment time of 3-6 weeks. Several randomized controlled trials (RCTs) demonstrated that postoperative WBI after BCS significantly decreased the risk of local (in-breast) recurrence and improved breast cancer mortality as well as survival. However, one of the most common side-effects of radiotherapy is fatigue, which is reported in up to 80% of cancer patients during treatment. Especially in early-stage breast cancer patients it might be the only serious side-effect following adjuvant irradiation, as fatigue often significantly reduces quality of life due to resulting functional impairment and psychological distress. Fatigue additionally has a distinct socioeconomic impact: 75% of patients and 40% of caregivers are forced to change their employment status due to cancer-related fatigue. For reducing treatment-related toxicity, several RCTs consequently addressed the question whether adjuvant WBI could be omitted in early-stage, low risk breast cancer patients treated with endocrine therapy. However, all these trials detected up to seven-time increased local recurrence rates without WBI following BCS. Both, longer duration of radiotherapy and larger radiation field sizes are known to be associated with increase in treatment-related fatigue. Accelerated partial breast irradiation (APBI), delivered exclusively to the original tumor location and not to the surrounding breast tissue, might therefore be an alternative treatment option with fewer side-effects for early-stage, low risk breast cancer patients. Few previous trials have already reported comparable outcomes for highly selected low-risk breast cancer patients for APBI compared to conventional WBI. First results also point out that APBI compared to WBI might be associated with less severity and intensity of fatigue. One method for APBI is single-dose intraoperative radiotherapy (IORT) delivered directly to the tumor after resection. Data is still limited for APBI, hence current international and German guidelines suggest the use of APBI for low-risk early stage breast cancer patients but recommend the application of APBI preferably within a clinical trial.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Fatigue 12 weeks

  Assessment of fatigue from baseline (before treatment start) compared to 12 weeks after treatment start as assessed by the FACIT (Functional Assessment of Cancer Therapy) Fatigue Assessment Questionnaire. Scale ranges from 0 (no fatigue) to 52 (maximum fatigue).

  12 weeks

Secondary Outcomes (14)

• Fatigue 5 weeks, 6 months, 2 years, 5 years after treatment start

  5 weeks, 6 months, 2 years, 5 years after treatment start

• Local tumor control in the index quadrant of the breast

  2 years and 5 years after treatment start

• Local tumor control in the ipsilateral breast

  2 years and 5 years after treatment start

• Quality of life employing EORTC (European Organisation for Research and Treatment of Cancer) Quality of life questionnaires (QLQ)-C30

  5 weeks, 12 weeks, 6 months, 2 years, 5 years after treatment start

• Quality of life employing BREAST-Q questionnaire

  5 weeks, 12 weeks, 6 months, 2 years, 5 years after treatment start

Other Outcomes (1)

• Explorative Endpoint

  after surgery

Study Arms (2)

BCS + WBI

ACTIVE COMPARATOR

breast conserving surgery followed by whole breast irradiation

Radiation: whole breast irradiation

BCS + IORT

EXPERIMENTAL

Breast conserving surgery incl intraoperative radiotherapy

Radiation: intraoperative radiotherapy

Interventions

intraoperative radiotherapy RADIATION

IORT with 21 Gy prescribed to the 90% isodose line

Also known as: IORT

BCS + IORT

whole breast irradiation RADIATION

hypofractionated WBI Total dose 40.05 Gy (15 x 2.67 Gy)

Also known as: WBI

BCS + WBI

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive breast cancer
• Total tumor size \< 2.5 cm
• cN0
• estrogen receptor positive, HER2-receptor negative on immunohistochemistry
• age \>= 50 years
• ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 2
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

You may not qualify if:

• Extensive microcalcifications
• Invasive lobular carcinoma
• Clinically involved lymph nodes
• No invasive axillary lymph node staging planned
• Patients with significant mental or physical comorbidities that preclude regular follow-up
• Neoadjuvant chemotherapy or neoadjuvant endocrine therapy
• previous radiotherapy of the breast
• Known carcinoma \< 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
• Pregnant or lactating women
• Participation in another competing clinical study or observation period of competing trials

Sponsors & Collaborators

• University Hospital Heidelberg: lead

Study Sites (1)

University Hospital of Heidelberg, Radiation Oncology

Heidelberg, 69120, Germany

Location

Related Publications (1)

• Forster T, Jakel C, Akbaba S, Krug D, Krempien R, Uhl M, Hafner MF, Konig L, Koerber SA, Harrabi S, Bernhardt D, Behnisch R, Krisam J, Hennigs A, Sohn C, Heil J, Debus J, Horner-Rieber J. Fatigue following radiotherapy of low-risk early breast cancer - a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419). Radiat Oncol. 2020 Jun 1;15(1):134. doi: 10.1186/s13014-020-01581-9.

  PMID: 32487184 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 12, 2019
• Study Start: October 1, 2019
• Primary Completion: March 16, 2026
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

DE (1)