COntinue the SaMe Systemic Therapy After Local Ablative Therapy for Oligo Progression in Metastatic Breast Cancer - the COSMO Study

Study Overview
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Brief Summary
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Patients with oligoprogression of metastatic breast cancer during palliative treatment that is amenable to local therapy will be included. The local ablative therapy (LAT) may consist of stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy, surgery or radiofrequency ablation (RFA).

Official Title
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COntinue the SaMe Systemic Therapy After Local Ablative Therapy for Oligo Progression in Metastatic Breast Cancer - the COSMO Study

Conditions
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Metastatic Cancer, Oligoprogressive, Breast Cancer Invasive

Intervention / Treatment
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* Procedure: Surgery
* Radiation: Radiotherapy
* Other: Radiofrequent ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast cancer MBC according to TNM-staging Oligoprogression defined as one or two distant metastatic lesions, limited to one organ, or the primary tumor or locoregional lymph nodes, increasing ≥20% in size and be larger than 15 mm or if metabolic activity increases (with 20% in SUVmax) on FDG-PET-CT. Systemic treatment can be either endocrine, targeted, chemotherapy or immune-checkpoint blockade Oligoprogression should occur during first- or second-line systemic therapy Patients should be on systemic therapy for at least six months. Status should be stable disease or partial or complete response for at least 6 months. Oligoprogression has to be detected with radiological imaging comparing the lesion on the same type of imaging modality as has been used at the start of systemic therapy. The radiological imaging that shows progression must be performed within 49 (+/- 3) days prior to registration. Bone metastases are classified as progressive if the lytic component of the lesion increases by ≥20% or the FDG-uptake increases by ≥20% on FDG-PET-CT Oligo-progression has to be confirmed with a FDG-PET-CT-scan 6 weeks (42 days) after the first screening scan. Lesion(s) must be amenable to resection, radiotherapy or radiofrequency ablation with the intent of local obliteration Age ≥18 World Health Organization (WHO) Performance Status 0 or 1 Signed written informed consent before patient registration according to ICH/GCP, and national/local regulations Exclusion Criteria: Having received more than two lines of systemic therapy for MBC If a treatment regimen has been de-escalated without adding other therapies, this is seen as one line of therapy. For example: Pertuzumab/trastuzumab+docetaxel followed by pertuzumab/trastuzumab will be viewed as one line of systemic therapy. Other malignancy except carcinoma in situ and basal-cell and squamous cell carcinoma of the skin, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiation therapy Current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection Presence of any medical condition that would place the patient at unusual risk, up to the discretion of the clinician Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Interventional Model Description: Lesion(s) will be treated with surgery, radiotherapy or radiofrequent ablation depending on the location. The treatment is standard of care and will be decided in the treating team of the patient.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Surgery, radiotherapy or radiofrequent ablation<br>The oligoprogresive lesion(s) will be treated with Surgery, radiotherapy or radiofrequent ablation depending on the location of the lesion. treatment will be standard of care and will be decided by the treating team of the patient. | Procedure: Surgery<br>* resection of the oligometastatic lesion(s)<br>Radiation: Radiotherapy<br>* radiation of the oligometastatic lesion(s)<br>Other: Radiofrequent ablation<br>* radiofrequent ablation of the oligometastatic lesion(s)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients free of progression at 6 months | progression-free survival at 6 months (PFS-6) | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients free of progression at 6 months per histoligical subtype | PFS-6 for breast cancer subtypes: ER+/HER2- vs. HER2+ vs. TN | At 6 months | 
| Number of patients free of progression at 6 months per breast cancer subtype | PFS-6, stratified by breast cancer subtype - localization of progressive lesion | At 6 months | 
| Number of patients free of progression at 6 months per localization of progressive lesion | PFS at 6 months separately for localization of progressive lesion: locoregional vs. cranial vs. visceral vs. bone | At 6 months | 
| Overall Surival (OS) | Evaluation of overall survival measured from baseline till death due to any cause | Up to 120 months | 
| Time to next line of treatment | Time to next line of systemic therapy meeasured from baseline | Up to 120 months | 
| Number of patients who develop visceral crisis | number of patients who develop visceral crisis | Up to 120 months | 
| Number of patients who develop complications after local ablative treatment | Assess the number of patients who develop complications after local ablative treatment | Up to 120 months |