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Praegnant Breast Cancer: Early/Advanced/Metastatic (PRAEGNANT)

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ClinicalTrials.gov Identifier: NCT02338167
Recruitment Status : Recruiting
First Posted : January 14, 2015
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Tuebingen

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.


Condition or disease Intervention/treatment
Advanced/Metastatic Breast Cancer Breast Cancer (Early Breast Cancer) Procedure: Blood sampling

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 13500 participants
Observational Model: Case-Only
Time Perspective: Other
Target Follow-Up Duration: 60 Months
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 Start Date : June 2014
Estimated Primary Completion Date : March 2026
Estimated Study Completion Date : March 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment
Advanced/metastatic breast cancer
3,500 patients with locally advanced, inoperable/metastatic breast cancer in any line of treatment (e.g. 1st, 2nd, 3rd, or ≥ 4th line).
Procedure: Blood sampling
A blood sample will be taken during a routine blood draw

Early breast cancer
10,000 patients with breast cancer in the neoadjuvant and adjuvant (early breast cancer) setting independent of treatment regimen.
Procedure: Blood sampling
A blood sample will be taken during a routine blood draw




Primary Outcome Measures :
  1. MBC (Metastatic Breast Cancer): Discovery of biomarkers, which predict progression free survival (PFS) [ Time Frame: PFS defined as the time to the first progression after study inclusion from the last time of progression before or at study entry ]
    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.

  2. EBC (Early Breast Cancer): Assessment of disease free sur-vival (DFS) [ Time Frame: up to 60 months ]
    DFS defined as the time to the first disease recurrence after study inclusion from time of primary diagnosis before or at study entry


Secondary Outcome Measures :
  1. MBC: Assessment of overall survival (OS) [ Time Frame: 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.

  2. MBC: Assessment of breast cancer specific survival (BCSS) [ Time Frame: Time to death from the date of the last progression before or at study entry. ]
    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.

  3. MBC: Objective response [ Time Frame: up to 60 months ]
    Objective response is defined as the best-documented response to the therapy started at study entry or the last therapy started before study entry.

  4. MBC: Description of therapies used in the metastatic setting [ Time Frame: after 60 months (after study completion) ]
    Therapies will be categorized and descriptive statistics will be presented.

  5. MBC: Quality of life [ Time Frame: 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 ]
    Assessed with EORTC QlQ-C30 and Visual Analog Scala

  6. MBC: Therapy adherence [ Time Frame: up to 60 months ]
    Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect.

  7. MBC: Influencing Factors of Depression in patients with metastatic breast cancer [ Time Frame: 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 ]
    Depression will be assessed by patient reported questionnaires e.g. CESD-R.

  8. MBC: Incidence of adverse events, serious adverse events will be reported. [ Time Frame: up to 60 months ]
    According to NCI Common Toxicity Criteria Version 4.03.

  9. MBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. [ Time Frame: Once at end of study ]
    Number of patients who will receive molecular testing results compared to the total number of included patients.

  10. MBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) [ Time Frame: Once at end of study ]
    Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening.

  11. MBC: Health economics for women with metastatic and/or locally advanced, inoperable breast cancer. [ Time Frame: 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 ]
    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.

  12. MBC: Patient reported influencing factors on therapy adherence in patients metastatic and/or locally advanced, inoperable breast cancer. [ Time Frame: 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 ]
    Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires.

  13. EBC: Assessment of distant disease-free survival (DDFS) [ Time Frame: Up to 60 months ]
    DDFS defined as the time to the first distant disease recurrence after study inclusion from time of primary diagnosis before or at study entry.

  14. EBC: Quality of life [ Time Frame: 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 ]
    Assessed with EORTC QLQ C-30 (Version 3.0), EORTC QLQ-BR23 and the EQ-Visual Analog Scale (VAS)

  15. EBC: Assessment of overall survival (OS) [ Time Frame: 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 primary diagnosis before or at study entry.

  16. EBC: Assessment of breast cancer specific survival (BCSS) [ Time Frame: Time to death due to breast cancer from the date of the primary diagnosis before or at study entry. ]
    BCSS is defined as the time to death due to breast cancer from the date of the primary diagnosis before or at study entry.

  17. EBC: Description of therapies used in the early breast cancer setting [ Time Frame: after 60 months (after study completion) ]
    Therapies will be categorized, and descriptive statistics will be presented.

  18. EBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. [ Time Frame: Once at end of study ]
    Number of patients who will receive molecular testing results compared to the total number of included pa-tients.

  19. EBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) [ Time Frame: Once at end of study ]
    Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening.

  20. EBC: Therapy adherence [ Time Frame: up to 60 months ]
    Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect

  21. EBC: Health economics for women with breast cancer [ Time Frame: up to 60 months ]
    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.

  22. EBC: Influencing Factors of Depression in patients with breast cancer [ Time Frame: 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 ]
    Depression will be assessed by patient reported ques-tionnaires e.g. CESD-R.

  23. EBC: Patient reported influencing factors on therapy adherence in patients with early breast cancer. [ Time Frame: 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 ]
    Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires.

  24. EBC: Incidence of adverse events, serious ad-verse events will be reported. [ Time Frame: up to 60 months ]
    NCI Common Toxicity Criteria Version 4.03.


Other Outcome Measures:
  1. Correlation of the incidence of depression with germline gentic variation and therapies and gene expression from leukocytes. [ Time Frame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 ]
    Depression Inventory values will be associated with blood biomarkers, single nucleotide polymorphisms and therapies.

  2. 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. [ Time Frame: after 60 months (after study completion) ]
    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.

  3. Correlation of gene alterations (mutations and or amplifications) and gene expres-sion between primary tumor, metastatic tumor and circulating tumor cells (CTCs). [ Time Frame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 ]
    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.

  4. Correlation of gene alterations (mutations and or amplifications) between primary tumor, metastatic tumor and circulating tumor DNA. [ Time Frame: after 60 months (after study completion) ]
    Circulating DNA (ctDNA) will be analyzed for genetic variation and compared to mutations assessed from FFPE tumor material.

  5. Prediction of therapy response, prognosis and side effects with germline Single Nucleotid Polymorphisms [ Time Frame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60 ]
    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.

  6. Correlation of blood protein biomarkers with side effects, and progression. [ Time Frame: Study entry and following a change of a therapy line (event-associated, e.g. after progression) up to month 60. ]
    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.

  7. Identification of risk factors for the development of metastatic disease in healthy women. [ Time Frame: after 60 months (after study completion) ]
    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.

  8. Influencing Factors of Physical Activity, Mental factors and Nutrition in patients with metastatic breast cancer [ Time Frame: 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 ]
    Physical activity and nutrition will be assessed with patient reported questionnaires, e.g. IPAQ and ER2.

  9. Time to progression from the beginning of subsequent therapy lines until the next progression. [ Time Frame: up to 60 months ]
    All molecular and other measures that might predict prognosis will be associated with the-se times to progression as well.

  10. Time to death from the beginning of subsequent therapy lines [ Time Frame: up to 60 months ]
    All molecular and other measures that might predict prognosis will be associated with these times to death as well.


Biospecimen Retention:   Samples With DNA
Blood samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338167


Contacts
Layout table for location contacts
Contact: Erik Belleville, PhD +49 931 359200 ext 36 belleville@clin-sol.com

  Show 58 Study Locations
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
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Principal Investigator: Diethelm Wallwiener, Prof. Dr. Universitätsfrauenklinik Tübingen
Principal Investigator: Peter Fasching, Prof. Dr. Frauenklinik des Universitätsklinikums Erlangen
Principal Investigator: Sara Brucker, Prof. Dr. Universitätsfrauenklinik Tübingen
Principal Investigator: Hans Tesch, Prof. Dr. Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus
Principal Investigator: Andreas Schneeweiss, Prof. Dr. Nationales Centrum für Tumorerkrankungen (NCT) Sektion Gynäkologische Onkologie

Additional Information:
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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT02338167     History of Changes
Other Study ID Numbers: SEN-01/14
First Posted: January 14, 2015    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases