Reaching for Evidence-baSed Chemotherapy Use in Endocrine Sensitive Breast Cancer

Estrogen Receptor Positive Tumor Clinical Trial

— RESCUE  

Official title:

Prospective Assessment of Disease Progression in Primary Breast Cancer Patients Undergoing EndoPredict® Gene Expression Testing - a Care Research Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03503799
• Other study ID #: NOGGO B3
• Status: Active, not recruiting
• Start date: July 17, 2018
• Est. completion date: October 1, 2032

Study information

• Verified date: November 2023
• Source: North Eastern German Society of Gynaecological Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Systematic assessment of survival data of patients who have been tested with EndoPredict®; prospective proof that patients with low risk classification by EndoPredict® (EPclin) can safely forgo chemotherapy and be treated with endocrine therapy alone.

Description:

The goal of the study is to receive current and comprehensive information about the diseasefree (remote metastasis free and recurrence free) interval of EndoPredict® low risk patients.

The study is organized and managed by the NOGGO e.V. (North Eastern German Society of Gynaecological Oncology e.V.) study coordination office under the existing and efficient infrastructure. All patients who receive gene expression analysis with EndoPredict® and satisfy the remaining inclusion / exclusion criteria may participate in the study. Data collection is prospective and non-interventional. The recruitment of the required patients is expected to take a maximum of 36 months .

It must be emphasized that the study is data collection only and not an interventional study. This means that the choice and implementation of the therapy as well as the treatment assessments and frequency during and after the treatment can only be determined by the Investigator.

The decision to participate in the study is independent of the patient´s therapy within the framework of a study. Patient data will be recorded at the time of inclusion and once a year thereafter. Patient follow-up will be by phone from the second year onward.

Primary objective is to show that female patients who have been tested as "low risk" by EPclin and have been treated with endocrine therapy only for at least 5 years have a 10-year DMFS rate > 90% (lower boundary of the one-sided 95% confidence interval).

Secondary objectives comprise the evaluation of DMFS (distant metastasis free survival) , DFS (disease free survival) and OS (overall survival) rates at different time points and for different groups. Assessment of the given chemotherapy regimens and the given endocrine therapy will be performed and the proportions of patients will be determined with respect to the received treatment and its duration in different groups. Furthermore, the proportion of patients in whom the tumor board recommendation follows the EndoPredict® result and the proportion of patients actually treated according to EndoPredict® result will be determined.

The association between outcome and treatment, EPclin, EP, and classical prognostic factors will be investigated in different groups of patients. The correlation and concordance between EPclin calculations derived from biopsies and surgical specimens will be assessed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1191
• Est. completion date: October 1, 2032
• Est. primary completion date: October 1, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent

2. Tested with EndoPredict within the previous 6 months before inclusion

3. Age = 18 years

4. Patients with primary invasive breast cancer, Stage I/II

5. ER-positive

6. HER2-negative

7. N0 or N1 (1-3 positive lymph nodes)

8. T1 - T3

Exclusion Criteria:

1. Inflammatory breast cancer

2. Bilateral breast cancer

3. Breast cancer in the last 10 years

4. Other invasive malignancies in the last 5 years

Related Conditions & MeSH terms

• Breast Neoplasms
• Estrogen Receptor Positive Tumor
• Human Epidermal Growth Factor Receptor 2 Negative Tumor
• Primary Invasive Breast Cancer

Intervention

Other:
• Observation
Visit 1 Informed consent Medical history Demographics Result of EndoPredict® Test Status of menopause Disease status Tumor board decision Planned anti-tumor-therapy Visit 2, 1 year after inclusion This visit will be documented at the study site Status of menopause Disease status Anti-tumor therapy Survival Following visits For these visits, patients will be asked directly through the Center for Clinical Trials of the Philipps-University Marburg (KKS Marburg) via phone. Status of Menopause Disease status Anti-tumor therapy Survival Treatment after end of the study The patient will be treated during and after end of study by physician's choice.

Locations

Country	Name	City	State
Germany	ANregiomed Ansbach	Ansbach
Germany	DRK Kliniken Köpenick	Berlin
Germany	Helios Klinikum Berlin Buch	Berlin
Germany	MVZ Hellersdorf - Zweigstelle Biesdorf	Berlin
Germany	Park-Klinik Weißensee	Berlin
Germany	Vivantes Klinikum am Urban	Berlin
Germany	Charité - Universitätsmedizin Berlin	Berlin-Mitte
Germany	Klinikum Bremerhaven Reinkenheide	Bremerhaven
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Krankenhaus St. Joseph Stift Dresden GmbH	Dresden
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Evangelisches Krankenhaus	Düsseldorf
Germany	Kreisklinik Ebersberg	Ebersberg
Germany	Klinikum Erding	Erding
Germany	Praxis Dr. Heinrich	Fürstenwalde
Germany	Krankenhaus St. Elisabeth und St. Barbara	Halle
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Krankenhaus Jerusalem	Hamburg
Germany	Mathilden Hospital	Herford
Germany	Frauenärzte am Bahnhofsplatz	Hildesheim
Germany	Universitätsklinikum Jena	Jena
Germany	Gemeinschaftsklinikum Mittelrhein gGmbH Kemperhof	Koblenz
Germany	VK & K Studien GbR	Landshut
Germany	Klinikum Magdeburg gGmbH	Magdeburg
Germany	Krankenhaus St. Marienstift	Magdeburg
Germany	Klinikum Fichtelgebirge	Marktredwitz
Germany	Frauenklinik der Technischen Universität München	München	Bayern
Germany	Gemeinschaftspraxis Gynäkologie Arabella	München
Germany	Oberhavel Kliniken GmbH	Oranienburg
Germany	Regioklinik Pinneberg	Pinneberg
Germany	Ernst von Bergmann Klinikum	Potsdam
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	RoMed Klinikum Rosenheim	Rosenheim
Germany	Klinikum Traunstein	Traunstein
Germany	Klinikum Mutterhaus der Borromäerinnen gGmbH	Trier
Germany	Harzklinikum Dorothea Christiane Erxleben	Wernigerode
Germany	Helios Universitätsklinikum Wuppertal	Wuppertal
Switzerland	Brustzentrum Bern Lindenhofgruppe	Bern
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Spital Zollikerberg	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
North Eastern German Society of Gynaecological Oncology	Center for Clinical Trials Philipps University Marburg

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (15)

Buus R, Sestak I, Kronenwett R, Denkert C, Dubsky P, Krappmann K, Scheer M, Petry C, Cuzick J, Dowsett M. Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy. J Natl Cancer Inst. 2016 Jul 10;108(11):djw149. doi: 10.1093/jnci/djw149. Print 2016 Nov. — View Citation

Cobain EF, Hayes DF. Indications for prognostic gene expression profiling in early breast cancer. Curr Treat Options Oncol. 2015 May;16(5):23. doi: 10.1007/s11864-015-0340-x. — View Citation

Denkert C, Kronenwett R, Schlake W, Bohmann K, Penzel R, Weber KE, Hofler H, Lehmann U, Schirmacher P, Specht K, Rudas M, Kreipe HH, Schraml P, Schlake G, Bago-Horvath Z, Tiecke F, Varga Z, Moch H, Schmidt M, Prinzler J, Kerjaschki D, Sinn BV, Muller BM, Filipits M, Petry C, Dietel M. Decentral gene expression analysis for ER+/Her2- breast cancer: results of a proficiency testing program for the EndoPredict assay. Virchows Arch. 2012 Mar;460(3):251-9. doi: 10.1007/s00428-012-1204-4. Epub 2012 Feb 28. — View Citation

Denkert C, Pfitzner BM, Heppner BI, Dietel M. [Molecular pathology for breast cancer: Importance of the gene expression profile]. Pathologe. 2015 Mar;36(2):145-53. doi: 10.1007/s00292-015-0009-z. German. — View Citation

Dubsky P, Brase JC, Jakesz R, Rudas M, Singer CF, Greil R, Dietze O, Luisser I, Klug E, Sedivy R, Bachner M, Mayr D, Schmidt M, Gehrmann MC, Petry C, Weber KE, Fisch K, Kronenwett R, Gnant M, Filipits M; Austrian Breast and Colorectal Cancer Study Group (ABCSG). The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer. 2013 Dec 10;109(12):2959-64. doi: 10.1038/bjc.2013.671. Epub 2013 Oct 24. — View Citation

Dubsky P, Filipits M, Jakesz R, Rudas M, Singer CF, Greil R, Dietze O, Luisser I, Klug E, Sedivy R, Bachner M, Mayr D, Schmidt M, Gehrmann MC, Petry C, Weber KE, Kronenwett R, Brase JC, Gnant M; Austrian Breast and Colorectal Cancer Study Group (ABCSG). EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer. Ann Oncol. 2013 Mar;24(3):640-7. doi: 10.1093/annonc/mds334. Epub 2012 Oct 3. — View Citation

Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5. — View Citation

Ettl J, Klein E, Hapfelmeier A, Grosse Lackmann K, Paepke S, Petry C, Specht K, Wolff L, Hofler H, Kiechle M. Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1. PLoS One. 2017 Sep 6;12(9):e0183917. doi: 10.1371/journal.pone.0183917. eCollection 2017. — View Citation

Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF, Dietze O, Greil R, Jelen A, Sevelda P, Freibauer C, Muller V, Janicke F, Schmidt M, Kolbl H, Rody A, Kaufmann M, Schroth W, Brauch H, Schwab M, Fritz P, Weber KE, Feder IS, Hennig G, Kronenwett R, Gehrmann M, Gnant M; EP Investigators. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011 Sep 15;17(18):6012-20. doi: 10.1158/1078-0432.CCR-11-0926. Epub 2011 Aug 1. — View Citation

Fitzal F, Filipits M, Rudas M, Greil R, Dietze O, Samonigg H, Lax S, Herz W, Dubsky P, Bartsch R, Kronenwett R, Gnant M. The genomic expression test EndoPredict is a prognostic tool for identifying risk of local recurrence in postmenopausal endocrine receptor-positive, her2neu-negative breast cancer patients randomised within the prospective ABCSG 8 trial. Br J Cancer. 2015 Apr 14;112(8):1405-10. doi: 10.1038/bjc.2015.98. Epub 2015 Mar 24. — View Citation

Kronenwett R, Bohmann K, Prinzler J, Sinn BV, Haufe F, Roth C, Averdick M, Ropers T, Windbergs C, Brase JC, Weber KE, Fisch K, Muller BM, Schmidt M, Filipits M, Dubsky P, Petry C, Dietel M, Denkert C. Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test. BMC Cancer. 2012 Oct 5;12:456. doi: 10.1186/1471-2407-12-456. — View Citation

Martin M, Brase JC, Calvo L, Krappmann K, Ruiz-Borrego M, Fisch K, Ruiz A, Weber KE, Munarriz B, Petry C, Rodriguez CA, Kronenwett R, Crespo C, Alba E, Carrasco E, Casas M, Caballero R, Rodriguez-Lescure A. Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial. Breast Cancer Res. 2014 Apr 12;16(2):R38. doi: 10.1186/bcr3642. — View Citation

Muller BM, Brase JC, Haufe F, Weber KE, Budzies J, Petry C, Prinzler J, Kronenwett R, Dietel M, Denkert C. Comparison of the RNA-based EndoPredict multigene test between core biopsies and corresponding surgical breast cancer sections. J Clin Pathol. 2012 Jul;65(7):660-2. doi: 10.1136/jclinpath-2012-200716. Epub 2012 Mar 23. — View Citation

Muller BM, Keil E, Lehmann A, Winzer KJ, Richter-Ehrenstein C, Prinzler J, Bangemann N, Reles A, Stadie S, Schoenegg W, Eucker J, Schmidt M, Lippek F, Johrens K, Pahl S, Sinn BV, Budczies J, Dietel M, Denkert C. The EndoPredict Gene-Expression Assay in Clinical Practice - Performance and Impact on Clinical Decisions. PLoS One. 2013 Jun 27;8(6):e68252. doi: 10.1371/journal.pone.0068252. Print 2013. — View Citation

Poremba C, Uhlendorff J, Pfitzner BM, Hennig G, Bohmann K, Bojar H, Krenn V, Brase JC, Haufe F, Averdick M, Dietel M, Kronenwett R, Denkert C. Preanalytical variables and performance of diagnostic RNA-based gene expression analysis in breast cancer. Virchows Arch. 2014 Oct;465(4):409-17. doi: 10.1007/s00428-014-1652-0. Epub 2014 Sep 14. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Distant metastasis free survival	To show that female patients who have been tested as "low risk" by EndoPredict® (EPclin) and have been treated with endocrine therapy only for at least 5 years have a 10-year distant metastasis-free survival (DMFS) > 90 % (lower boundary of the one-sided 95 % confidence interval)	10 years
Secondary	DMFS "low risk"	Assessment of DMFS of patients with EPclin "low risk" (or EP "low risk" [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	DFS "low risk"	Assessment of DFS of patients with EPclin "low risk" (or EP "low risk" [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	OS "low risk"	Assessment of OS of patients with EPclin "low risk" (or EP "low risk" [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	DMFS "high risk"	Assessment of DMFS of patients with EPclin "high risk" in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	DFS "high risk"	Assessment of DFS of patients with EPclin "high risk" in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	OS "high risk"	Assessment of OS of patients with EPclin "high risk" in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment).	3, 5 and 10 years
Secondary	DMFS "high risk + low risk"	DMFS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2).	3, 5 and 10 years
Secondary	DFS "high risk + low risk"	DFS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2).	3, 5 and 10 years
Secondary	OS "high risk + low risk"	OS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2).	3, 5 and 10 years
Secondary	Portion of patients tumor board follows the EndoPredict® result	Assessment of the proportion of patients in whom the tumor board follows the EndoPredict® result in regard to treatment recommendation (in all patients and separately for men and women).	1 year
Secondary	Portion of patient treated according EndoPredict® result	Assessment of the proportion of patients who were actually treated according to the EndoPredict® result (in all patients and separately for men and women).	1 year
Secondary	Prognostic Performance of classical prognostic factors compared to EndoPredict®	Assessment of the classical prognostic factors tumor size, nodal status, grading, quantitative estrogen receptor, quantitative progesterone receptor and quantitative Ki67 and evaluation of their prognostic performance compared to EPclin and EP in univariate and multivariate analyses of DMFS, DFS, OS (in all patients, separately for men and women, only in patients who have been treated according to the EndoPredict® result).	3, 5 and 10 years
Secondary	DMFS "low risk vs. high risk"	Assessment of DMFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC (immunohistochemistry)-classification.	3, 5 and 10 years
Secondary	DFS "low risk vs. high risk"	Assessment of DFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification.	3, 5 and 10 years
Secondary	OS "low risk vs. high risk"	Assessment of OS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification.	3, 5 and 10 years
Secondary	DMFS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors	Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of DMFS of patients with ki67-values low (= 10%)/ intermediate (11-24%)/ high (= 25%) and EPclin low risk vs high risk.	3, 5 and 10 years
Secondary	DFS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors	Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of DFS of patients with ki67-values low (= 10%)/ intermediate (11-24%)/ high (= 25%) and EPclin low risk vs high risk.	3, 5 and 10 years
Secondary	OS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors	Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of OS of patients with ki67-values low (= 10%)/ intermediate (11-24%)/ high (= 25%) and EPclin low risk vs high risk.	3, 5 and 10 years
Secondary	DMFS "low risk vs. high risk" who have /have not been treated according to the S3 and St. Gallen guidelines	Assessment of DMFS after 3, 5 and 10 years of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification.	3, 5 and 10 years
Secondary	DFS "low risk vs. high risk" who have /have not been treated according to the S3 and St. Gallen guidelines	Assessment of DFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification.	3, 5 and 10 years
Secondary	OS "low risk vs. high risk" who have /have not been treated according to the S3 and St. Gallen guidelines	Assessment of OS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification.	3, 5 and 10 years
Secondary	Chemotherapy regimens	Description of the given chemotherapy regimens (in all patients and separately for men and women).	1 year
Secondary	Given endocrine therapy	Description of the given endocrine therapy (in all patients and separately for men and women).	10 years
Secondary	Duration of endocrine therapy	Duration of the endocrine therapy (in all patients and separately for men and women).	10 years
Secondary	Proportion of patients with prolonged endocrine therapy	Proportion of patients with EPclin "low risk" and "high risk" respectively who received an extended (> 5 years) endocrine therapy in all patients and separately for men and women).	10 years
Secondary	DMFS for patients with 5 years of endocrine therapy vs. extended endocrine therapy	Assessment of DMFS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years).	10 years
Secondary	DFS for patients with 5 years of endocrine therapy vs. extended endocrine therapy	Assessment of DFS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years).	10 years
Secondary	OS for patients with 5 years of endocrine therapy vs. extended endocrine therapy	Assessment of OS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years).	10 years
Secondary	Correlation ( pT- and pN data vs. ciT and ciN-data)	Assessment of the correlation between EPclin, that has been calculated with pT- (pathological tumor size) and pN (pathological nodal status) data and the EPclin based on ciT (clinical/ imaging tumor size) and ciN (clinical/imaging nodal status)-data (in all patients and separately for men and women).	1 year
Secondary	Concordance ( pT- and pN data vs. ciT and ciN-data)	Assessment of the concordance between EPclin, that has been calculated with pT- and pN data and the EPclin based on ciT and ciN-data (in all patients and separately for men and women).	1 year