Advanced/Metastatic Breast Cancer Clinical Trial
— PRAEGNANTOfficial 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
| NCT number | NCT02338167 |
| Other study ID # | SEN-01/14 |
| Secondary ID | |
| Status | Recruiting |
| Phase | |
| First received | |
| Last updated | |
| Start date | June 2014 |
| Est. completion date | March 2027 |
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.
| Status | Recruiting |
| Enrollment | 13500 |
| Est. completion date | March 2027 |
| Est. primary completion date | March 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Uniklinik RWTH Aachen | Aachen | Nordrhein-Westfalen |
| Germany | Gesundheitszentrum St. Marien GmbH | Amberg | Bayer |
| Germany | Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg | Aschaffenburg | Bayern |
| Germany | Hämatologische-onkologische Praxis | Augsburg | Bayern |
| Germany | Klinikum Augsburg | Augsburg | Bayern |
| Germany | Sozialstiftung Bamberg Klinikum am Bruderwald | Bamberg | Bayern |
| Germany | Klinikum Bayreuth | Bayreuth | Bayern |
| Germany | Charité | Berlin | |
| Germany | Klinik für Gynäkologie und Geburtshilfe, Helios Kliniken | Berlin | |
| Germany | Klinikum Sindelfingen-Böblingen gGmbH | Böblingen | Baden-Württemberg |
| Germany | Gynäkologie und Geburtshilfe im medizinischen Zentrum Bonn | Bonn | Nordrhein-Westfalen |
| Germany | Marienhospital | Bottrop | Nordrhein-Westfalen |
| Germany | Klinikum Chemnitz gGmbH | Chemnitz | Sachsen |
| Germany | Klinikum Darmstadt Frauenklinik | Darmstadt | Hessen |
| Germany | DONAUISAR Klinikum | Deggendorf | Bayern |
| Germany | Onkologisches Zentrum Donauwörth | Donauwörth | Bayern |
| Germany | Universitätsklinik Dresden | Dresden | Sachsen |
| Germany | Universitätsfrauenklinik Düsseldorf | Düsseldorf | Nordrhein-Westfalen |
| Germany | Rottal-Inn-Kliniken GmbH | Eggenfelden | Bayern |
| Germany | Universitätsfrauenklinik Erlangen | Erlangen | Bayern |
| Germany | Kliniken Essen-Mitte | Essen | Nordrhein-Westfalen |
| Germany | Centrum für Hämatologie und Onkologie Bethanien | Frankfurt | Hessen |
| Germany | Klinik für Frauenheilkunde, Universitätsklinikum Freiburg | Freiburg | Baden-Württemberg |
| Germany | Praxis für Frauenheilkunde und Geburtshilfe | Fürstenwalde | Brandenburg |
| Germany | Klinikum Fürth | Fürth | Bayern |
| Germany | Niels-Stensen-Kliniken | Georgsmarienhütte | Niedersachsen |
| Germany | Universitätsklinikum Halle (Saale) | Halle | Sachsen-Anhalt |
| Germany | Onkologie Lerchenfeld | Hamburg | |
| Germany | Universitätsklinikum Hamburg-Eppendorf | Hamburg | |
| Germany | NCT Heidelberg | Heidelberg | Baden-Württemberg |
| Germany | Schwerpunktpraxis für Hämatologie und Onkologie | Kaiserslautern | Rheinland-Pfalz |
| Germany | Frauenklinik der St. Vincentius-Kliniken gAG | Karlsruhe | Baden-Württemberg |
| Germany | St. Vincentius-Kliniken gAG | Karlsruhe | Baden-Württenmberg |
| Germany | Klinikum Kassel GmbH | Kassel | Hessen |
| Germany | Christian-Albrechts-Universität Kiel | Kiel | Christian-Albrechts-Universität Kiel |
| Germany | Klinik für Gynäkologie und Geburtshilfe | Kiel | Schleswig-Holstein |
| Germany | Institut für Versorgungsforschung in der Onkologie GbR | Koblenz | Nordrhein-Westfalen |
| Germany | Gemeinschaftspraxis für Hämatologie und Onkologie | Langen | Hessen |
| Germany | Onkologische Schwerpunktpraxis Leer-Emden | Leer | Niedersachsen |
| Germany | Universitäres Krebszentrum Leipzig | Leipzig | Sachsen |
| Germany | Universitätsklinikum Schleswig-Holstein | Lübeck | Schleswig-Holstein |
| Germany | Praxisklinik am Rosengarten | Mannheim | Baden-Württemberg |
| Germany | Institut für Versorgungsforschung | Mayen | Rheinland-Pfalz |
| Germany | Frauenklinik und Poliklinik der Technischen Universität München | München | Bayern |
| Germany | Klinikum der Universität München Frauenklinik | München | Bayern |
| Germany | Ruppiner Kliniken GmbH, Hochschulklinikum der Med. Hochschule Brandenburg | Neuruppin | Brandenburg |
| Germany | medius Klinik Nürtingen | Nürtingen | Baden-Württemberg |
| Germany | St. Vincenz-Krankenhaus GmbH | Paderborn | Nordrhein-Westfalen |
| Germany | Praxis Onkologie und Hämatologie | Recklinghausen | Nordrhein-Westfalen |
| Germany | Caritas-Krankenhaus St. Josef | Regensburg | Bayern |
| Germany | Paracelsus Krankenhaus Ruit | Ruit | Baden-Württemberg |
| Germany | g.SUND Gynäkologie Kompetenzzentrum Stralsund | Stralsund | Mecklenburg-Vorpommern |
| Germany | Kreiskrankenhaus Torgau | Torgau | Sachsen |
| Germany | Universitätsfrauenklinik Tübingen | Tübingen | Baden-Württemberg |
| Germany | Universitätsfrauenklinik Ulm | Ulm | Baden-Württemberg |
| Germany | Klinikum Wetzlar | Wetzlar | Hessen |
| Germany | Lahn-Dill-Kliniken GmbH Klinikum Wetzlar | Wetzlar | Hessen |
| Germany | Gesellschaft für Medizinische Studien Würselen | Würselen | Nordrhein-Westfalen |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital Tuebingen |
Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Correlation of the incidence of depression with germline gentic variation and therapies and gene expression from leukocytes. | Depression Inventory values will be associated with blood biomarkers, single nucleotide polymorphisms and therapies. | Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 | |
| Other | 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. | DNA and RNA of the primary tumor will be extracted of archival formalin fixed, paraffin embedded tumor samples and analyzed mutations, mutation changes, and differentially expressed genes. Additionally, FFPE will be used for the construction of a TMA for antibody staining. | after 60 months (after study completion) | |
| Other | Correlation of gene alterations (mutations and or amplifications) and gene expres-sion between primary tumor, metastatic tumor and circulating tumor cells (CTCs). | Circulating tumor cells (CTC) from selected patients will be analyzed for mutations and gene amplifications. Findings will be compared to mutations assessed from FFPE tumor material. | Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 | |
| Other | Correlation of gene alterations (mutations and or amplifications) between primary tumor, metastatic tumor and circulating tumor DNA. | Circulating DNA (ctDNA) will be analyzed for genetic variation and compared to mutations assessed from FFPE tumor material. | after 60 months (after study completion) | |
| Other | Prediction of therapy response, prognosis and side effects with germline Single Nucleotid Polymorphisms | Germline DNA will be used as reference for the genetic analysis of the tumor, CTCs and ctDNA. Additionally ge-nome-wide SNPs will be assessed and used for a ge-nome-wide association study. | Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 | |
| Other | Correlation of blood protein biomarkers with side effects, and progression. | EGFR (1068), HSP27 (pS78), IL-1a, IL-1b, IL-2, IL-6, Il-8, PAI-1, sEGFR, ERK1/2, mTOR, TNF-a, TNF-b. P1NP, CTX, Vitamin D, PTH, OPG, RANKL, Sclerostin, DKK-1. | Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60. | |
| Other | Identification of risk factors for the development of metastatic disease in healthy women. | Patients will be matched to a pool of controls, which are not part of the PRAEGNANT study, but which have been recruited during the same time. | after 60 months (after study completion) | |
| Other | Influencing Factors of Physical Activity, Mental factors and Nutrition in patients with metastatic breast cancer | Physical activity and nutrition will be assessed with patient reported questionnaires, e.g. IPAQ and ER2. | 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 | |
| Other | Time to progression from the beginning of subsequent therapy lines until the next progression. | All molecular and other measures that might predict prognosis will be associated with the-se times to progression as well. | up to 60 months | |
| Other | Time to death from the beginning of subsequent therapy lines | All molecular and other measures that might predict prognosis will be associated with these times to death as well. | up to 60 months | |
| Primary | MBC (Metastatic Breast Cancer): Discovery of biomarkers, which predict progression free survival (PFS) | Analyses will be done separately for each therapy line. Biomarkers include gene expression profiling of the primary tumor and the corresponding metastases, somatic mutations, germline genetic variation, epigenetic changes and miRNA variation up to a total of 500,000 biomarkers. | PFS defined as the time to the first progression after study inclusion from the last time of progression before or at study entry | |
| Primary | EBC (Early Breast Cancer): Assessment of disease free sur-vival (DFS) | DFS defined as the time to the first disease recurrence after study inclusion from time of primary diagnosis before or at study entry | up to 60 months | |
| Secondary | MBC: Assessment of overall survival (OS) | OS is defined as the time to death from the date of the last progression before or at study entry. | OS is defined as the time to death from the date of the last progression before or at study entry. | |
| Secondary | MBC: Assessment of breast cancer specific survival (BCSS) | BCSS is defined as the time to to death due to breast cancer from the date of the last progression before or at study entry. | Time to death from the date of the last progression before or at study entry. | |
| Secondary | MBC: Objective response | Objective response is defined as the best-documented response to the therapy started at study entry or the last therapy started before study entry. | up to 60 months | |
| Secondary | MBC: Description of therapies used in the metastatic setting | Therapies will be categorized and descriptive statistics will be presented. | after 60 months (after study completion) | |
| Secondary | MBC: Quality of life | Assessed with EORTC QlQ-C30 and Visual Analog Scala | 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 | |
| Secondary | MBC: Therapy adherence | Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect. | up to 60 months | |
| Secondary | MBC: Influencing Factors of Depression in patients with metastatic breast cancer | Depression will be assessed by patient reported questionnaires e.g. CESD-R. | 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 | |
| Secondary | MBC: Incidence of adverse events, serious adverse events will be reported. | According to NCI Common Toxicity Criteria Version 4.03. | up to 60 months | |
| Secondary | MBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. | Number of patients who will receive molecular testing results compared to the total number of included patients. | Once at end of study | |
| Secondary | MBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) | Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening. | Once at end of study | |
| Secondary | MBC: Health economics for women with metastatic and/or locally advanced, inoperable breast cancer. | EORTC QLQ C-30 (Version 3.0) (among others) and actu-al documented costs of diagnostic procedures, therapies, treatment of side effects and care for tumor-associated symptoms will be used to calculate health care costs, quality adjusted life years (QALY) and incremental cost effectiveness ratios (ICER) between patient groups. | 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 | |
| Secondary | MBC: Patient reported influencing factors on therapy adherence in patients metastatic and/or locally advanced, inoperable breast cancer. | Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires. | 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 | |
| Secondary | EBC: Assessment of distant disease-free survival (DDFS) | DDFS defined as the time to the first distant disease recurrence after study inclusion from time of primary diagnosis before or at study entry. | Up to 60 months | |
| Secondary | EBC: Quality of life | Assessed with EORTC QLQ C-30 (Version 3.0), EORTC QLQ-BR23 and the EQ-Visual Analog Scale (VAS) | 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 | |
| Secondary | EBC: Assessment of overall survival (OS) | OS is defined as the time to death from the date of the primary diagnosis before or at study entry. | OS is defined as the time to death from the date of the last progression before or at study entry. | |
| Secondary | EBC: Assessment of breast cancer specific survival (BCSS) | BCSS is defined as the time to death due to breast cancer from the date of the primary diagnosis before or at study entry. | Time to death due to breast cancer from the date of the primary diagnosis before or at study entry. | |
| Secondary | EBC: Description of therapies used in the early breast cancer setting | Therapies will be categorized, and descriptive statistics will be presented. | after 60 months (after study completion) | |
| Secondary | EBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. | Number of patients who will receive molecular testing results compared to the total number of included pa-tients. | Once at end of study | |
| Secondary | EBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) | Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening. | Once at end of study | |
| Secondary | EBC: Therapy adherence | Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect | up to 60 months | |
| Secondary | EBC: Health economics for women with breast cancer | EORTC QLQ C-30 (Version 3.0) (among others) and actu-al documented costs of diagnostic procedures, thera-pies, treatment of side effects and care for tumor-associated symptoms will be used to calculate health care costs, quality adjusted life years (QALY) and incre-mental cost effectiveness ratios (ICER) between patient groups. | up to 60 months | |
| Secondary | EBC: Influencing Factors of Depression in patients with breast cancer | Depression will be assessed by patient reported ques-tionnaires e.g. CESD-R. | 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 | |
| Secondary | EBC: Patient reported influencing factors on therapy adherence in patients with early breast cancer. | Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires. | 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 | |
| Secondary | EBC: Incidence of adverse events, serious ad-verse events will be reported. | NCI Common Toxicity Criteria Version 4.03. | up to 60 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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