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

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).

Study Overview

• Status: Recruiting
• Conditions: Oligoprogressive; Metastatic Cancer; Breast Cancer Invasive
• Intervention / Treatment: Procedure: Surgery; Radiation: Radiotherapy; Other: Radiofrequent ablation

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: G Sonke, MD; Phone Number: 9111 +31-20-512; Email: g.sonke@nki.nl
• Study Contact Backup: Name: A Almekinders; Email: c.almekinders@nki.nl

Study Locations

• Netherlands
  • Alkmaar, Netherlands
    • Not yet recruiting
    • Noordwest Ziekenhuisgroep
    • Contact: S Vrijaldenhoven, MD
  • Amsterdam, Netherlands
    • Recruiting
    • Antoni van Leeuwenhoek
    • Contact: G Sonke, MD; Email: g.sonke@nki.nl
    • Contact: A Almekinders, MD; Email: c.almekinders@nki.nl
    • Contact: G Sonke, MD
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate
    • Contact: K J Beelen, MD; Phone Number: +31880058888; Email: info@rijnstate.nl
    • Contact: K J Beelen, MD
  • Deventer, Netherlands
    • Not yet recruiting
    • Deventer Ziekenhuis
    • Contact: A Imholz, MD
  • Goes, Netherlands
    • Recruiting
    • ADRZ
    • Contact: E van Vliet, MD; Phone Number: +31881250000; Email: researchbureau@adrz.nl
    • Contact: E van Vliet, MD
  • Groningen, Netherlands
    • Not yet recruiting
    • Martini Ziekenhuis
    • Contact: A van der Velden, MD
  • Utrecht, Netherlands
    • Not yet recruiting
    • Antonius Ziekenhuis
    • Contact: M Agterof, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Surgery, radiotherapy or 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.	Procedure: Surgery; resection of the oligometastatic lesion(s); Radiation: Radiotherapy; radiation of the oligometastatic lesion(s); Other: Radiofrequent ablation; radiofrequent ablation of the oligometastatic lesion(s)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Maarten van de Weijden Foundation
• Investigators: Principal Investigator: G Sonke, The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): April 1, 2035
• Study Completion (Estimated): April 1, 2040

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: M21CSM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: to be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No