Clinical trial NCT02338167: Praegnant Breast Cancer: Early/Advanced/Metastatic
Official title: Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Adjuvant and Advanced/Metastatic Setting: Health Care Research, Pharmacogenomics, Biomarkers, Health Economics
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Advanced/Metastatic Breast Cancer
Breast Cancer (Early Breast Cancer)
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 13500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 10,000 patients with breast cancer in the neoadjuvant and adjuvant (early breast cancer) setting independent of treatment regimen.

3500 patients with locally advanced/metastatic breast cancer in any line of treatment (e.g. 1st, 2nd, 3rd, or ≥ 4th line). A patient can only participate after providing informed consent.

Brief summary: Among patients with breast cancer the subgroup of patients with metastases are considered the group of patients with the worst prognosis. Not only regard-ing therapy decisions but also with regard to quality assured healthcare and health economics this entity of patients remains a challenge.

Recently, novel advances in breast cancer therapy aim at the targeted therapy of tumor entities and identification of patients, for whom the greatest therapy benefit, and the least side effects are expected.

However molecular assessment of the patient and the tumor in the metastatic situation is not performed on a routine basis and in many cases tumor character-istics from the primary tumor are considered reliable enough to make therapy decisions for the metastatic patients. Although molecular reassessment of tu-mor characteristics from tumor material of the metastasis is recommended in national guidelines, only a minority of patients is biopsied, because of the inva-siveness of the procedure, even though biopsy related complications are reported to be rare.

With modern analytic methods from blood based biomaterial there seems to be an opportunity to correlate blood based tumor assessments with actual charac-teristics of the tumor. These include expression analysis, tumor mutation analy-sis, tumor gene copy number aberrations and others. One of the main aims of the PRAEGNANT study is therefore to establish an infrastructure for the compre-hensive analysis of tumor and metastatic molecular characteristics of the patient and the tumor.

Furthermore, health care related outcomes as well as health economics provide novel approaches for integration of patients in study conduct and health care awareness and are study aims of the PRAEGNANT study.


Eligibility criteria: Inclusion Criteria for the early breast cancer setting:

* Adult breast cancer patients (age ≥18 years)
* Patients with breast cancer and no evidence of distant metastases with a diagnosis not longer than 91 days before study entry
* Patients, who are able and willing to sign the informed consent form

Inclusion Criteria for the advanced/metastatic setting:

* Adult women aged ≥18 years
* Patients with the diagnosis of invasive breast cancer (in German: Mammakarzinom, as op-posed to "non-invasive"= ductales Carcinoma in situ; irrespective of status of BC, e.g. TNM, re-ceptor status etc.) and
* Patients, who are willing and able to sign the informed consent form
* Patients with metastatic or locally advanced, inoperable disease proven by clinical measures (i.e. standard imaging)

Exclusion Criteria:

* Patients who did not sign the informed consent form
* Patients, who are not eligible for observation due to non-availability and/or severe comor-bidities as evaluated by the treating physician

Primary outcomes:
measure: MBC (Metastatic Breast Cancer): Discovery of biomarkers, which predict progression free survival (PFS)
timeFrame: PFS defined as the time to the first progression after study inclusion from the last time of progression before or at study entry
measure: EBC (Early Breast Cancer): Assessment of disease free sur-vival (DFS)
timeFrame: up to 60 months
Secondary outcomes:
measure: MBC: Assessment of overall survival (OS)
timeFrame: OS is defined as the time to death from the date of the last progression before or at study entry.
measure: MBC: Assessment of breast cancer specific survival (BCSS)
timeFrame: Time to death from the date of the last progression before or at study entry.
measure: MBC: Objective response
timeFrame: up to 60 months
measure: MBC: Description of therapies used in the metastatic setting
timeFrame: after 60 months (after study completion)
measure: MBC: Quality of life
timeFrame: Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: MBC: Therapy adherence
timeFrame: up to 60 months
measure: MBC: Influencing Factors of Depression in patients with metastatic breast cancer
timeFrame: Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: MBC: Incidence of adverse events, serious adverse events will be reported.
timeFrame: up to 60 months
measure: MBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial.
timeFrame: Once at end of study
measure: MBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations)
timeFrame: Once at end of study
measure: MBC: Health economics for women with metastatic and/or locally advanced, inoperable breast cancer.
timeFrame: Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: MBC: Patient reported influencing factors on therapy adherence in patients metastatic and/or locally advanced, inoperable breast cancer.
timeFrame: Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: EBC: Assessment of distant disease-free survival (DDFS)
timeFrame: Up to 60 months
measure: EBC: Quality of life
timeFrame: Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: EBC: Assessment of overall survival (OS)
timeFrame: OS is defined as the time to death from the date of the last progression before or at study entry.
measure: EBC: Assessment of breast cancer specific survival (BCSS)
timeFrame: Time to death due to breast cancer from the date of the primary diagnosis before or at study entry.
measure: EBC: Description of therapies used in the early breast cancer setting
timeFrame: after 60 months (after study completion)
measure: EBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial.
timeFrame: Once at end of study
measure: EBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations)
timeFrame: Once at end of study
measure: EBC: Therapy adherence
timeFrame: up to 60 months
measure: EBC: Health economics for women with breast cancer
timeFrame: up to 60 months
measure: EBC: Influencing Factors of Depression in patients with breast cancer
timeFrame: Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: EBC: Patient reported influencing factors on therapy adherence in patients with early breast cancer.
timeFrame: Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: EBC: Incidence of adverse events, serious ad-verse events will be reported.
timeFrame: up to 60 months
Other outcomes:
measure: Correlation of the incidence of depression with germline gentic variation and therapies and gene expression from leukocytes.
timeFrame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60
measure: Correlation of gene alterations (mutations and or amplifications) and gene expres-sion between primary tumor and metastatic tumor for the prediction of side effects and prognosis.
timeFrame: after 60 months (after study completion)
measure: Correlation of gene alterations (mutations and or amplifications) and gene expres-sion between primary tumor, metastatic tumor and circulating tumor cells (CTCs).
timeFrame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60
measure: Correlation of gene alterations (mutations and or amplifications) between primary tumor, metastatic tumor and circulating tumor DNA.
timeFrame: after 60 months (after study completion)
measure: Prediction of therapy response, prognosis and side effects with germline Single Nucleotid Polymorphisms
timeFrame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60
measure: Correlation of blood protein biomarkers with side effects, and progression.
timeFrame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60.
measure: Identification of risk factors for the development of metastatic disease in healthy women.
timeFrame: after 60 months (after study completion)
measure: Influencing Factors of Physical Activity, Mental factors and Nutrition in patients with metastatic breast cancer
timeFrame: Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent
measure: Time to progression from the beginning of subsequent therapy lines until the next progression.
timeFrame: up to 60 months
measure: Time to death from the beginning of subsequent therapy lines
timeFrame: up to 60 months
Locations:
city: Böblingen
country: Germany
facility: Klinikum Sindelfingen-Böblingen gGmbH
state: Baden-Württemberg
city: Freiburg
country: Germany
facility: Klinik für Frauenheilkunde, Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: NCT Heidelberg
state: Baden-Württemberg
city: Karlsruhe
country: Germany
facility: Frauenklinik der St. Vincentius-Kliniken gAG
state: Baden-Württemberg
city: Mannheim
country: Germany
facility: Praxisklinik am Rosengarten
state: Baden-Württemberg
city: Nürtingen
country: Germany
facility: medius Klinik Nürtingen
state: Baden-Württemberg
city: Ruit
country: Germany
facility: Paracelsus Krankenhaus Ruit
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Universitätsfrauenklinik Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
state: Baden-Württemberg
city: Karlsruhe
country: Germany
facility: St. Vincentius-Kliniken gAG
state: Baden-Württenmberg
city: Aschaffenburg
country: Germany
facility: Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg
state: Bayern
city: Augsburg
country: Germany
facility: Hämatologische-onkologische Praxis
state: Bayern
city: Augsburg
country: Germany
facility: Klinikum Augsburg
state: Bayern
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg Klinikum am Bruderwald
state: Bayern
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth
state: Bayern
city: Deggendorf
country: Germany
facility: DONAUISAR Klinikum
state: Bayern
city: Donauwörth
country: Germany
facility: Onkologisches Zentrum Donauwörth
state: Bayern
city: Eggenfelden
country: Germany
facility: Rottal-Inn-Kliniken GmbH
state: Bayern
city: Erlangen
country: Germany
facility: Universitätsfrauenklinik Erlangen
state: Bayern
city: Fürth
country: Germany
facility: Klinikum Fürth
state: Bayern
city: München
country: Germany
facility: Klinikum der Universität München Frauenklinik
state: Bayern
city: München
country: Germany
facility: Frauenklinik und Poliklinik der Technischen Universität München
state: Bayern
city: Regensburg
country: Germany
facility: Caritas-Krankenhaus St. Josef
state: Bayern
city: Amberg
country: Germany
facility: Gesundheitszentrum St. Marien GmbH
state: Bayer
city: Fürstenwalde
country: Germany
facility: Praxis für Frauenheilkunde und Geburtshilfe
state: Brandenburg
city: Neuruppin
country: Germany
facility: Ruppiner Kliniken GmbH, Hochschulklinikum der Med. Hochschule Brandenburg
state: Brandenburg
city: Kiel
country: Germany
facility: Christian-Albrechts-Universität Kiel
state: Christian-Albrechts-Universität Kiel
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt Frauenklinik
state: Hessen
city: Frankfurt
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
state: Hessen
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH
state: Hessen
city: Langen
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
state: Hessen
city: Wetzlar
country: Germany
facility: Klinikum Wetzlar
state: Hessen
city: Wetzlar
country: Germany
facility: Lahn-Dill-Kliniken GmbH Klinikum Wetzlar
state: Hessen
city: Stralsund
country: Germany
facility: g.SUND Gynäkologie Kompetenzzentrum Stralsund
state: Mecklenburg-Vorpommern
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken
state: Niedersachsen
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis Leer-Emden
state: Niedersachsen
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Gynäkologie und Geburtshilfe im medizinischen Zentrum Bonn
state: Nordrhein-Westfalen
city: Bottrop
country: Germany
facility: Marienhospital
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
facility: Universitätsfrauenklinik Düsseldorf
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
state: Nordrhein-Westfalen
city: Herne
country: Germany
state: Nordrhein-Westfalen
city: Koblenz
country: Germany
facility: Institut für Versorgungsforschung in der Onkologie GbR
state: Nordrhein-Westfalen
city: Paderborn
country: Germany
facility: St. Vincenz-Krankenhaus GmbH
state: Nordrhein-Westfalen
city: Recklinghausen
country: Germany
facility: Praxis Onkologie und Hämatologie
state: Nordrhein-Westfalen
city: Würselen
country: Germany
facility: Gesellschaft für Medizinische Studien Würselen
state: Nordrhein-Westfalen
city: Kaiserslautern
country: Germany
facility: Schwerpunktpraxis für Hämatologie und Onkologie
state: Rheinland-Pfalz
city: Mayen
country: Germany
facility: Institut für Versorgungsforschung
state: Rheinland-Pfalz
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
state: Sachsen
city: Dresden
country: Germany
facility: Universitätsklinik Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Universitäres Krebszentrum Leipzig
state: Sachsen
city: Torgau
country: Germany
facility: Kreiskrankenhaus Torgau
state: Sachsen
city: Kiel
country: Germany
facility: Klinik für Gynäkologie und Geburtshilfe
state: Schleswig-Holstein
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité
city: Berlin
country: Germany
facility: Klinik für Gynäkologie und Geburtshilfe, Helios Kliniken
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Onkologie Lerchenfeld
Study officials:
affiliation: Universitätsfrauenklinik Tübingen
name: Diethelm Wallwiener, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Frauenklinik des Universitätsklinikums Erlangen
name: Peter Fasching, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsfrauenklinik Tübingen
name: Sara Brucker, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus
name: Hans Tesch, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nationales Centrum für Tumorerkrankungen (NCT) Sektion Gynäkologische Onkologie
name: Andreas Schneeweiss, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muller V, Hein A, Hartkopf AD, Fasching PA, Kolberg HC, Hadji P, Tesch H, Haberle L, Ettl J, Luftner D, Wallwiener M, Beckmann MW, Schneeweiss A, Belleville E, Uhrig S, Wimberger P, Hielscher C, Meyer J, Wurmthaler LA, Kurbacher CM, Wuerstlein R, Untch M, Janni W, Taran FA, Lux MP, Wallwiener D, Brucker SY, Fehm TN, Michel LL. Occurrence and characteristics of patients with de novo advanced breast cancer according to patient and tumor characteristics - A retrospective analysis of a real world registry. Eur J Cancer. 2022 Sep;172:13-21. doi: 10.1016/j.ejca.2022.05.015. Epub 2022 Jun 18.
citation: Hein A, Hartkopf AD, Emons J, Lux MP, Volz B, Taran FA, Overkamp F, Hadji P, Tesch H, Haberle L, Ettl J, Luftner D, Wurmthaler LA, Wallwiener M, Muller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Kurbacher CM, Wuerstlein R, Thomssen C, Untch M, Fasching PA, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Kolberg HC. Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status. Eur J Cancer. 2021 Sep;155:1-12. doi: 10.1016/j.ejca.2021.06.033. Epub 2021 Jul 23.
citation: Huebner H, Kurbacher CM, Kuesters G, Hartkopf AD, Lux MP, Huober J, Volz B, Taran FA, Overkamp F, Tesch H, Haberle L, Luftner D, Wallwiener M, Muller V, Beckmann MW, Belleville E, Ruebner M, Untch M, Fasching PA, Janni W, Fehm TN, Kolberg HC, Wallwiener D, Brucker SY, Schneeweiss A, Ettl J. Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany. BMC Cancer. 2020 Nov 11;20(1):1091. doi: 10.1186/s12885-020-07546-1.