Standard Surveillance vs. Intensive Surveillance in Early Breast Cancer

ConditionBreast Cancer

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18-75

SponsorProf. Wolfgang Janni

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.

Unilateral or bilateral primary invasive carcinoma of the breast, confirmed histologically.

Patients with intermediate- to high-risk early breast cancer defined as either

an indication for (neo-)adjuvant chemotherapy (regardless whether performed or not), and/or

Disqualifiers

in situ carcinoma of the cervix or

adequately treated basal cell carcinoma of the skin or

ipsi- or contralateral non-invasive carcinoma of the breast (DCIS).

Patients in pregnancy or breastfeeding. If a patient gets pregnant during the participation in the interventional phase of the study (Year 1-5), an end of intervention visit will be scheduled and the patient will enter the follow-up phase of the study. Pregnancy during the follow-up phase of the study is to be reported but does not lead to an exclusion of the study.

Trial design

Design model

Parallel

Treatments tested in this trial

Determination of tumormarkers (CA27.29, CEA, CA125)
Diagnostic test
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.
Determination of CTC levels
Diagnostic test
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-.
Determination of ctDNA levels
Diagnostic test
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.
Biobanking of blood samples
Other intervention
To ensure the possibility of retrospective studies during and after the ongoing study, a biobank will be implemented.

Treatment groups

3,500 Participants

are divided into 2 treatment groups

Group A: Intensive Surveillance armActive comparator 3 interventions

Group B: Standard Surveillance armPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Overall Survival (OS)

OS is defined as time from randomization until the death of the patient independent of cause of death. If a patient is not known to have died, OS is censored at the date of last contact.

Time frame

10 years

Overall Lead Time Effect

This endpoint is a composite measure, defined as the median time from molecular to via Imaging verified Recurrence Lead Time (calculated only for patients in the liquid-biopsy guided Intensive Surveillance arm) + Difference in time to distant recurrence between the two arms (i.e., difference between median time from randomization to distant recurrence for all patients with distant recurrence in the Standard Surveillance arm and median time from randomization to distant recurrence for all patients with distant recurrence in the liquid-biopsy guided Intensive Surveillance arm). The Overall Lead Time Effect will be assessed for all markers in combination.

Time frame

5 years

Secondary outcomes

Invasive disease-free survival (IDFS)

IDFS is defined as time from randomization until first IDFS event, including any invasive ipsilateral, regional, contralateral, and distant disease recurrence, second primary tumors, or death from any cause as event; non-invasive, in-situ cancer events are excluded. If a patient has not had an event, IDFS is censored at the date of last adequate tumor assessment.

Time frame

10 years

Distant disease-free survival (DDFS)

DDFS is defined as time from randomization until first DDFS event including metastasis, second primary tumors and death from any cause as event. If a patient has not had an event, DDFS is censored at the date of last adequate tumor assessment.

Time frame

10 years

Distant recurrence-free survival (DRFS)

DRFS is defined as time from randomization until first DRFS event including metastasis and second primary tumors; death from any cause is not included as event. If a patient has not had an event, DRFS is censored at the date of last adequate tumor assessment.

Time frame

10 years

Breast cancer specific survival (BCSS)

BCSS is defined as time from randomization until breast cancer associated death of the patient. If a patient is not known to have died, BCSS is censored at the date of last contact. If a patient has died for reasons not associated with breast cancer (by clinical assessment), BCSS is censored at the date of death.

Time frame

10 years

Other outcomes

Establishment of a Biobank for Translational Research Endpoint

A biobank will allow the storage of unused biomaterials from both, the Intensive Surveillance arm as well as the Standard Surveillance arm. These materials will be used for future retrospective studies.

Time frame

5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Prof. Wolfgang Janni

Lead sponsor

University of Ulm

Sponsor institution

German Federal Ministry of Education and Research

Collaborator

Source ClinicalTrials.gov

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