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

Phase 2

Recruiting

• Conditions: Breast Cancer Invasive; Metastatic Cancer; Oligoprogressive
• Interventions: Procedure: Surgery; Radiation: Radiotherapy; Other: Radiofrequent ablation

• Registration Number: NCT05301881
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-21
• Study First Submitted QC: 2022-03-21
• Study First Posted: 2022-03-31
• Study Start: 2023-04-17
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-05
• Primary Completion: 2035-04-01
• Study Completion: 2040-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

• Histologically confirmed invasive breast cancer
• Metastatic breast cancer
• 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
• 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 70days prior to LAT.
• 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 5-7 weeks after the initial scan that showed oligoprogression.
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Surgery, radiotherapy or radiofrequent ablation	Radiotherapy	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.
Surgery, radiotherapy or radiofrequent ablation	Surgery	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.
Surgery, radiotherapy or radiofrequent ablation	Radiofrequent ablation	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.

Primary Outcome Measures

Name	Time	Method
Number of patients free of progression at 6 months	At 6 months	progression-free survival at 6 months (PFS-6)

Secondary Outcome Measures

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

Trial Locations

Locations (7)

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

Rijnstate; 🇳🇱 Arnhem, Netherlands

Deventer ziekenhuis; 🇳🇱 Deventer, Netherlands

ADRZ; 🇳🇱 Goes, Netherlands

Martini ziekenhuis; 🇳🇱 Groningen, Netherlands

Antonius ziekenhuis; 🇳🇱 Utrecht, Netherlands