Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer

Study Overview
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Brief Summary
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The prognosis for patients with metastatic breast cancer has improved continuously. Systemic therapies alone are not able to cure the disease permanently. Investigators initiated this randomized controlled multinational and multicenter clinical trial to analyse the impact of a local metastases-directed radiotherapy in addition to standard systemic therapy in patients with oligometastatic breast cancer on progression-free survival and quality of life.

Detailed Description
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Preferably ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions. Larger lesions or lesions with critical normal tissue involvement should be treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in moderate hypofractionated radiotherapy (depending on the size and location of the target volume and the decision of the radiooncologist). For critical organs in the target volume, standard fractionated radiotherapy can be used.

Official Title
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Effectiveness and Tolerability of Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer: A Randomized Controlled Multinational and Multicenter Clinical Trial

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Radiation: Metastases-directed Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastasized breast cancer - up to 5 clinically manifest (new, progressive, persistent) metastases (a lymph node metastasis and a circumscribed local recurrence are each considered as one metastasis, i.e. also locoregional recurrent breast carcinomas with additional hematogenic metastasis possible) maximum of 3 cerebral metastases known indication for palliative drug therapy (endocrine therapy and/or chemotherapy and/or treatment with other substances) given according to guidelines (1st-line or further therapy lines, a special regime is not specified) Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 local radiation of all metastases possible presentation of a written declaration of consent patient ≥ 18 years Exclusion Criteria: Previous radiotherapy, if this interferes with treatment within the scope of the study symptomatic metastases requiring local therapy of all metastases (e.g. pain radiation), a radiation indication (or other local therapy) for individual metastases is not a criterion for exclusion known central nervous system (CNS) metastasis without extracerebral metastasis (in these cases, immediate local therapy is mandatory) more than three known CNS metastases (no indication for purely local therapy of only the metastases, primary whole brain radiation is indicated) multifocal metastasis in one organ with impossibility to comply with the dose constraints for this organ (e.g., no indication for local therapy of only the metastases, primary whole brain radiation is indicated) (e.g. in the liver) exclusively regional lymph node metastasis without haematogenic metastases (in these cases local therapy is clearly indicated according to guidelines) relevant comorbidity, if this results in restrictions for further therapy Incapacity to contract or lack of informed consent Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard<br>Standard of care, i. e. no local radiotherapy in addition to standard systemic therapy (exception: palliative local treatment of symptomatic lesions where indicated) | |
| Experimental: Experimental<br>Standard of care (standard systemic therapy) + study intervention | Radiation: Metastases-directed Radiotherapy<br>* Ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First co-primary outcome measure is progression-free survival (PFS) | Co-primary progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST) | at least 12 months after randomization | 
| Second co-primary outcome measure is quality of life | Co-primary quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer patients with 30 items (QLQ-C30) sum score | 12 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility (per-protocol within intention-to-treat) | Proportion of participants treated per protocol | 12 weeks | 
| Overall survival | Time between randomization and death | at least 1, up to 5 years | 
| Toxicity (number and degree of reported toxicities in both treatment arms) | Proportion of participants with degree of toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and by Radiation Treatment Oncology Group (RTOG) by point in time of follow-up with higher degree indicating higher intensity | 0 to 5 years | 
| Neoplasia-specific quality of life | Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for Cancer patients with 30 items (QLQ-C30) with different scales | quarterly up to 5 years | 
| Breast cancer-specific quality of life | Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for breast cancer patients with 23 items (QLQ-BR23) on 4-point Likert scales with different directions | quarterly up to 5 years | 
| Patient satisfaction | Research and Treatment of Cancer (EORTC) Patient satisfaction questionnaire for cancer patients with 33 items (PATSAT-C33) on 5-point Likert scale with higher scores indicating greater satisfaction | 12 weeks | 
| Frequency of adverse events | Number of patients with adverse and serious adverse events | 0 to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligometastatic Breast Cancer, Radiotherapy, Progression-free survival (PFS)