NCT05658172

Standard Surveillance vs. Intensive Surveillance in Early Breast Cancer

SURVIVE (Standard Surveillance vs. Intensive Surveillance in Early Breast Cancer) - a Partially Double-blinded, Multi-center, Randomized, Controlled Superiority Study

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 3,500 (estimated)
• Sponsor: Prof. Wolfgang Janni · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical study is to evaluate the potential benefits of intensified surveillance versus standard surveillance in medium-risk and high-risk early breast cancer patients. The main questions it aims to answer are: * Comparison of the 5-year ob´verall survival rates between patients in the Standard Surveillance arm versus patients in the liquid-biopsy guided Intensive Surveillance arm * Determination of the Overall Lead Time Effect generated due to tumor marker/CTC/ctDNA guided Intensive Surveillance compared to Standard Surveillance after primary therapy in early breast cancer patients. Participants will recieve regular blood drawals. Solely the blood samples of the intensive surveillance arm will be analysed for prospective tumor markers/CTCs/ctDNAs. Abnormal findings of either marker will trigger diagnostic imaging to search for possible metastases. The blood samples of the standard surveillance arm will solely be biobanked for future research purposes.

Detailed description

This is a partially double-blinded, multi-center, randomized, controlled superiority study to evaluate the potential benefits of intensified surveillance versus standard surveillance in medium-risk and high-risk early breast cancer patients. 3500 patients will be enrolled after completion of primary anti-tumor therapy (adjuvant chemotherapy, surgery or radiotherapy, whichever occurs last) and randomized in a 1:1 ratio to receive: * Standard Surveillance according to national guidelines or * Intensive Surveillance with additional testing of blood samples for prospective tumor markers (CA27.29, CA125, CEA), CTC and ctDNA In both study arms patients will receive standard surveillance according to national guidelines, including clinical follow-up visits every 3 months for the first 3 years and every 6 months for the following 2 years. Additionally, blood samples will be drawn and Quality of Life (QoL) will be analyzed at these clinical follow-up visits in both arms. In the Standard Surveillance arm blood samples will be stored in a biobank. In the Intensive Surveillance arm blood samples will be tested for prospective tumor markers (CA27.29, CA125, CEA), CTCs and ctDNA. Abnormal findings of either marker (CA27.29 or CA125 or CEA or CTC or ctDNA) will trigger diagnostic imaging. Additionally, blood samples will be stored in a biobank for retrospective analysis. In both study arms detection of distant recurrence will terminate the surveillance protocol and treatment will be initiated according to national guidelines. Planned enrollment period is approximately 24 months, total study duration is approximately 144 months (2-year recruitment period, 5-year interventional period, 5-year follow up period). In terms of long-term follow-up after end of study, patients have the possibility to participate in the patient self-reporting registry (Patientenselbstauskunft).

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Determination of tumormarkers (CA27.29, CEA, CA125)	CA27.29, CEA and CA125 will be measured with the AIA®-CL1200 by TOSOH BIOSCIENCE (TOSOH CORPORATION, Tokyo, Japan). The CL AIA-PACK assays are two-step chemiluminescence enzyme immunoassay kits. CA27.29/CEA/CA125 present in a test sample is bound to the anti- CA27.29/CEA/CA125 mouse monoclonal antibody immobilized on the magnetic microparticles in one cell (Cell-I). After first incubation, the magnetic microparticles are washed and the enzyme-labeled anti- CA27.29/CEA/CA125 mouse monoclonal antibody that has been reconstituted in another cell (Cell-II) is dispensed into Cell-I. After second incubation, the magnetic microparticles are washed again and are incubated with a chemiluminescent substrate, DIFURAT®. The amount of enzyme-labeled antibodies that bind to the magnetic microparticles is directly proportional to the CA27.29/CEA/CA125 concentration in the test sample. A standard curve is constructed, unknown sample concentrations are calculated by using this curve.
DIAGNOSTIC_TEST	Determination of CTC levels	CTCs will be analyzed using the CellSearch® System (Menarini Silicon Biosystems). The CellSearch® system is designed to enumerate CTCs of epithelial origin (CD45-, EpCAM+, cytokeratin 8+ / 18+ and/or 19+). The basic principle is linking a magnetic ferrofluid reagent that contains i. a. antibodies targeting the EpCAM antigen to CTCs. After steps of immunomagnetic capture and enrichment as well as addition of fluorescent reagents (that contain anti-CK-PE, DAPI and anti-CD45-APC), the automatic dispersion to a magnetic cartridge holder takes place. Via strong magnetic field, the magnetically labeled epithelial cells are attracted to the surface of the cartridge where they can be scanned automatically. Images of events where CK-PE and DAPI fluorescence are co-located are presented to the user for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45-.
DIAGNOSTIC_TEST	Determination of ctDNA levels	Presence of ctDNA will be analyzed centrally at Inivata Inc. using the RaDaRTM assay. Therefore, primary tumor tissue and peripheral blood specimens will be shipped for centralized analysis to Inivata Inc. RaDaRTM is a tumor-informed approach, beginning with whole exome sequencing of a tumor specimen from a patient's biopsy or surgical resection. SNVs and indels identified from the exome sequencing are prioritized to build a patient specific primer panel of up to 48 tumor-specific somatic variants. Patient specific primers are combined with common SNP primers for NGS for quality control purposes. To detect patient specific ctDNA, NGS testing is performed with the RaDaRTM assay using a multiplex PCR based on the InVision® platform.
OTHER	Biobanking of blood samples	To ensure the possibility of retrospective studies during and after the ongoing study, a biobank will be implemented.

Timeline

• Start date: 2022-12-07
• Primary completion: 2035-12-01
• Completion: 2035-12-01
• First posted: 2022-12-20
• Last updated: 2025-05-02

Locations

1 site across 1 country: Germany