The Symphony Triple A Study: Using Symphony in Treatment Decisions Concerning Adjuvant Systemic Therapy

NCT02209857 | Completed

• 1 other identifier: DIAK-TrA-20121
• Study Type: observational
• Target: 660
• Locations: 1 country
• Sites: 34

Brief Summary

Rationale: Prediction of prognosis in patients with breast cancer is important to determine the indication for adjuvant chemo-, endocrine- and immunotherapy. Apart from the clinicopathological parameters incorporated into the Adjuvant!Online predictive model, the validated 70-gene signature MammaPrint® is predictive of outcome too. MammaPrint® is advised in the current Dutch CBO guideline (2012) for hormone receptor positive, invasive ductal breast cancer in individual cases when there is 'doubt' about the indication for adjuvant chemotherapy based on traditional prognostic factors. In the present study MammaPrint® is used in this CBO 2012 guideline defined group of patients as an additional test for decision-making for adjuvant chemotherapy. Objective: To assess the impact of MammaPrint® on clinical decision making regarding the administration of adjuvant chemotherapy in the CBO 2012 guideline defined group of hormone receptor positive invasive ductal carcinoma patients when there is doubt about the indication for adjuvant chemotherapy based on traditional prognostic factors. The influence of various factors and the impact of MammaPrint® in predefined subgroups will be analyzed too. Data from a national registry regarding adjuvant systemic treatment in patients with similar clinicopathological characteristics in whom MammaPrint® was not used will be obtained to provide a control group. Hypothesis: In the group of patients where national guidelines advocate using systemic therapy but doctors are ambivalent in treating patients with adjuvant chemotherapy, it is hypothesized that using MammaPrint® as an additional test will change the indication for adjuvant therapy in a substantial proportion of patients resulting in at least 10% less patients who receive adjuvant chemotherapy. Thus, in the study group at least 10% less patients will receive chemotherapy when compared to a contemporary group of patients with similar clinicopathological characteristics but without using MammaPrint® Study population: Hormone receptor positive, invasive ductal breast cancer patients when there is doubt about the indication for adjuvant chemotherapy based on traditional prognostic factors. Study design: This is a prospective multicentre impact study.

Conditions

Breastcancer; Invasive Breast Carcinoma by Gene Expression Profile

Keywords

Breastcancer; Adjuvant chemotherapy; 70-gene expression profile; MammaPrint

Outcome Measures

Primary Outcomes (1)

• Frequency of adjuvant chemotherapy

  We will measure and compare the proportion of patients receiving adjuvant chemotherapy in the group of patients receiving MammaPrint and the group who doesn't receive MammaPrint. In addition we'll record the type of chemotherapy given.

  Within one month after surgery

Secondary Outcomes (5)

• Changes in adjuvant systemic treatment decisions due to MammaPrint use

  Within one month after (initial) surgery

• Influence of BluePrint and TargetPrint on adjuvant systemic treatment decisions

  Within one month after (initial) surgery

• Clinical utility of MammaPrint in multicentric/contralateral disease.

  Within one month after (initial) surgery

• Concordance of TargetPrint results with locally assessed ICH/FISH ER, PR and Her2 results

  Within one month after (initial) surgery

• Comparison of clinical subtype with BluePrint molecular subtype

  Within one month after (initial) surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population is the CBO 2012 guideline defined group of hormone receptor positive, invasive ductal breast cancer patients when there is doubt about the indication for adjuvant chemotherapy based on traditional prognostic factors. Patients are included and MammaPrint® is determined after complete histological assessment following definitive surgery. The following pathology items have to be recorded: tumour size, grade, ER- and PR- receptor status, Her-2 neu status, and lymph node status. No difference is made in ethnical background or past medical history other than cancer.

You may qualify if:

• Oestrogen receptor positive, invasive ductal and female breast cancer patients where the benefit of adjuvant chemotherapy is uncertain based on traditional prognostic factors
• Written informed consent
• Patients with multicentric or contralateral disease

You may not qualify if:

• Patients with a previous history of malignancy (in the five years before breast cancer diagnosis), excluding basal cell carcinoma.
• Patients with confirmed distant metastasis.
• Patients who undergo neoadjuvant systemic treatment.

Sponsors & Collaborators

• Diakonessenhuis, Utrecht: lead
• Agendia: collaborator

Study Sites (34)

Whilhelmina ziekenhuis

Assen, Drenthe, 9041RK, Netherlands

Location

Medisch Centrum Zuiderzee

Lelystad, Flevoland, 8233AA, Netherlands

Location

Gelre ziekenhuis

Apeldoorn, Gelderland, 7334 DZ, Netherlands

Location

Rijnstate

Arnhem, Gelderland, 6815AD, Netherlands

Location

Gederse Vallei

Ede, Gelderland, 6716RP, Netherlands

Location

Sint Jansdal

Harderwijk, Gelderland, 3844DG, Netherlands

Location

Ziekenhuis Rivierenland

Tiel, Gelderland, 4000 HA, Netherlands

Location

Gelre ziekenhuis

Zutphen, Gelderland, 7207 AE, Netherlands

Location

Jeroen Bosch ziekenhuis

's-Hertogenbosch, North Brabant, 5301EH, Netherlands

Location

Medisch Centrum Alkmaar

Alkmaar, North Holland, 1815JD, Netherlands

Location

Boven IJ ziekenhuis

Amsterdam, North Holland, 1034CS, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, North Holland, 1091AC, Netherlands

Location

Gemini ziekenhuis

Den Helder, North Holland, 1782GZ, Netherlands

Location

Kennemer Gasthuis

Haarlem, North Holland, 2035RC, Netherlands

Location

Spaarne ziekenhuis

Hoofddorp, North Holland, 2134TM, Netherlands

Location

Westfriesgasthuis

Hoorn, North Holland, 1624NP, Netherlands

Location

Waterland ziekenhuis

Purmerend, North Holland, 1441RN, Netherlands

Location

Vlietland ziekenhuis

Schiedam, North Holland, 3118 JH, Netherlands

Location

Zaans medisch centrum

Zaandam, North Holland, 1502DV, Netherlands

Location

Deventer ziekenhuis

Deventer, Overijssel, 7416SE, Netherlands

Location

Ropcke Zweers ziekenhuis

Hardenberg, Overijssel, 7772SE, Netherlands

Location

Isale klinieken

Zwolle, Overijssel, 8011 JW, Netherlands

Location

Nij Smellinghe ziekenhuis

Drachten, Provincie Friesland, 9202 NN, Netherlands

Location

Tjongerschans

Heerenveen, Provincie Friesland, 8441PW, Netherlands

Location

Antoniusziekenhuis

Sneek, Provincie Friesland, 8601ZK, Netherlands

Location

Martini ziekenhuis

Groningen, Provincie Groningen, 9728NT, Netherlands

Location

IJsselland ziekenhuis

Capelle aan den IJssel, South Holland, 2906ZC, Netherlands

Location

Sint Fransiscus gasthuis

Rotterdam, South Holland, 3045 PM, Netherlands

Location

Lange Land ziekenhuis

Zoetermeer, South Holland, 2700 KJ, Netherlands

Location

Alexander Monro ziekenhuis

Bilthoven, Utrecht, 3723 MB, Netherlands

Location

Ter Gooi ziekenhuis

Hilversum, Utrecht, 1201 DA, Netherlands

Location

Sint Antoniusziekenhuis

Nieuwegein, Utrecht, 3435CM, Netherlands

Location

Diakonessenziekenhuis

Utrecht, Utrecht, 3508 TG, Netherlands

Location

Zuwe Hofpoort ziekenhuis

Woerden, Utrecht, 3447GN, Netherlands

Location

Related Publications (12)

• Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N, Parker HL. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001 Feb 15;19(4):980-91. doi: 10.1200/JCO.2001.19.4.980.

  PMID: 11181660 BACKGROUND

• Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747-52. doi: 10.1038/35021093.

  PMID: 10963602 BACKGROUND

• van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002 Dec 19;347(25):1999-2009. doi: 10.1056/NEJMoa021967.

  PMID: 12490681 BACKGROUND

• van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002 Jan 31;415(6871):530-6. doi: 10.1038/415530a.

  PMID: 11823860 BACKGROUND

• Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92. doi: 10.1093/jnci/djj329.

  PMID: 16954471 BACKGROUND

• Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C, Meijers C, de Graaf PW, Bos MM, Hart AA, Rutgers EJ, Peterse JL, Halfwerk H, de Groot R, Pronk A, Floore AN, Glas AM, Van't Veer LJ, van de Vijver MJ. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2009 Oct;117(3):483-95. doi: 10.1007/s10549-008-0191-2. Epub 2008 Sep 26.

  PMID: 18819002 BACKGROUND

• Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A, Glas AM, Bogaerts J, Cardoso F, Piccart-Gebhart MJ, Rutgers ET, Van't Veer LJ; TRANSBIG Consortium. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat. 2009 Jul;116(2):295-302. doi: 10.1007/s10549-008-0130-2. Epub 2008 Jul 27.

  PMID: 18661261 BACKGROUND

• Knauer M, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ, Koornstra RH, Bueno-de-Mesquita JM, Linn SC, van 't Veer LJ. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010 Apr;120(3):655-61. doi: 10.1007/s10549-010-0814-2. Epub 2010 Mar 5.

  PMID: 20204499 BACKGROUND

• Mook S, Schmidt MK, Weigelt B, Kreike B, Eekhout I, van de Vijver MJ, Glas AM, Floore A, Rutgers EJT, van 't Veer LJ. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. 2010 Apr;21(4):717-722. doi: 10.1093/annonc/mdp388. Epub 2009 Oct 13.

  PMID: 19825882 BACKGROUND

• Mook S, Knauer M, Bueno-de-Mesquita JM, Retel VP, Wesseling J, Linn SC, Van't Veer LJ, Rutgers EJ. Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol. 2010 May;17(5):1406-13. doi: 10.1245/s10434-009-0902-x. Epub 2010 Jan 22.

  PMID: 20094918 BACKGROUND

• Bueno-de-Mesquita JM, van Harten WH, Retel VP, van 't Veer LJ, van Dam FS, Karsenberg K, Douma KF, van Tinteren H, Peterse JL, Wesseling J, Wu TS, Atsma D, Rutgers EJ, Brink G, Floore AN, Glas AM, Roumen RM, Bellot FE, van Krimpen C, Rodenhuis S, van de Vijver MJ, Linn SC. Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol. 2007 Dec;8(12):1079-1087. doi: 10.1016/S1470-2045(07)70346-7. Epub 2007 Nov 26.

  PMID: 18042430 BACKGROUND

• Drukker CA, Bueno-de-Mesquita JM, Retel VP, van Harten WH, van Tinteren H, Wesseling J, Roumen RM, Knauer M, van 't Veer LJ, Sonke GS, Rutgers EJ, van de Vijver MJ, Linn SC. A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer. 2013 Aug 15;133(4):929-36. doi: 10.1002/ijc.28082. Epub 2013 Mar 4.

  PMID: 23371464 BACKGROUND

Related Links

• Information concerning the MammaPrint 70-gene expression profile
• Current Dutch national guideline breast cancer

Biospecimen

Retention: SAMPLES WITH DNA

The tissue specimen for MammaPrint® analysis consists of a tumour block or 10 unstained slides with 5µm section on each slide. The tissue can be shipped as formalin fixed paraffin embedded (FFPE) tissue. For further information: www.agendia.com or www.symphonytripleA.nl.

Study Officials

• Thijs van Dalen, Dr

  Diakonessenhuis Utrecht, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: August 6, 2014
• Study Start: January 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: May 1, 2016
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

NL (34)