Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer (POSYTIVE)

Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer, a Multicenter Prospective Randomized Study to Evaluate the Use of Local Therapy

Primary Operation in synchronous metastasized invasive breast cancer to evaluate the use of local therapy

Study Overview

• Status: Completed
• Conditions: Circulating Tumor Cells; Synchronous Metastasized Breast Cancer
• Intervention / Treatment: Procedure: Surgery; Procedure: Surgery on Demand

Detailed Description

This study is a prospective, randomized, multicentre, study concerning the influence of local treatment on the patients with synchronous metastasized breast cancer. Patients will be stratified at inclusion according to the centre, the menopausal status (pre-menopausal, post-menopausal), the hormone-receptor status (ER-/PR-/not determinable; any PR and/or Er+), the HER-2 status (positive vs. negative/not determinable), the grading (G1/G2/not determinable vs. G3), location of metastases (visceral ± vs bone only), organs with metastases (single organ vs multiple organs) and use of first line chemotherapy (anthracycline ± vs. taxane vs others). Thereafter patients will be randomly assigned to receive either local therapy of the breast (lumpectomy or mastectomy + axillary surgery /± radiotherapy) versus no local therapy. Systemic therapy will be administered at the centers policy.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Paracelsus Medical University Salzburg-Oncology, Coop. Group
  • Vienna, Austria, 1090
    • Medical University of Vienna
  • Vienna, Austria, 1090
    • Medical University of Vienna-General Hospital Vienna
  • Burgenland
    • Guessing, Burgenland, Austria, 7540
      • Hospital Guessing
    • Oberpullendorf, Burgenland, Austria, 7350
      • Hospital Oberpullendorf
  • Carinthia
    • St. Veit a. d. Glan, Carinthia, Austria, 9300
      • Ordination Dr. Wette
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University Graz, Oncology
    • Graz, Styria, Austria, 8036
      • Gynaegological Medical University Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University of Innsbruck
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • General Hospital Linz
    • Linz, Upper Austria, Austria, 4010
      • Ordensklinikum Linz GmbH - BHS Linz, Coop. Study Group
    • Linz, Upper Austria, Austria, 4010
      • Ordensklinikum Linz GmbH - Elisabethinen Linz
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH
  • Vorarlberg
    • Feldkirch, Vorarlberg, Austria, 6807
      • State Hospital Feldkirch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients age ≥ 18 years
• Eastern Cooperative Oncology Group Performance Status is 0 -2
• Untreated synchronous metastasized invasive carcinoma of the breast with the primary tumor in situ (bilateral synchronous metastasized breast cancer patients are eligible)
• The primary tumor must be identified and may be any size, however, primary resection with resection free margins must be possible
• Invasive adenocarcinoma of the breast on histological examination
• The metastatic site must be identified by radiological assessment(Computer Tomography of the chest and the abdomen OR ultrasound and chest x ray for visceral metastases; bone scan AND/OR computer tomography AND/OR magnetic resonance for bone metastases). A biopsy is not necessary.
• Written informed consent must be obtained and documented prior to beginning any protocol specific procedures and according to local regulatory requirements
• able to comply with the protocol requirements during the treatment and follow-up period.

Exclusion Criteria:

• Patients in whom a R0 resection (microscopic free margins) is clinically questionable
• Inflammatory cancer
• Patients with a brain metastasis
• Patients who are not eligible for general anesthesia and operations
• Patients without metastatic breast cancer (patients with a tumor marker value (CEA, CA15-3) above normal levels without the radiological proven evidence of metastases are not eligible for the study)
• Patients with a second untreated malignancy
• Any previous malignancy treated with curative intent and the patient has not been disease-free for 5 years - exceptions are: (a)carcinoma in situ of the cervix, (b)squamous carcinoma of the skin, (c)basal cell carcinoma of the skin
• Patients with any recurrent cancer disease
• Pregnant or lactating women
• Patients are not allowed to be part of another local therapy trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A: Surgical Therapy; Local therapy consists of lumpectomy or mastectomy with or without radiotherapy (according to center tumor board decision) with a resection free margin of at least 1 mm or more demonstrated on paraffin embedded histological sections. Intraoperative frozen sections are allowed but not definitive for margin assessment. Sentinel node biopsy may be performed and has always to be followed by axillary dissection of level I and II (axillary surgery level I and II is mandatory).	Procedure: Surgery; lumpectomy or mastectomy with or without radiotherapy. Sentinel biopsy followed by axillary dissection (level I-II)
Other: B: Surgery on Demand; In Arm B (no local therapy) it may be necessary to perform local therapy on demand (surgery, radiotherapy). Reasons may be uncontrolled bleeding or infected exulcerations with a septic component and no treatment benefit from conservative therapy. This will be considered as protocol deviation. However, the patient's follow up is recorded and data are available for analyses as intention to treat.	Procedure: Surgery on Demand; if necessary local therapy on demand

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival with vs without local therapy (surgery)	Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Distant Progression	Time to distant progression with vs without local therapy (surgery)	Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months
Time to Local Progression (TTPl)	Time to local progression with vs without local therapy (surgery)	Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months

Collaborators and Investigators

• Sponsor: Austrian Breast & Colorectal Cancer Study Group
• Collaborators: Bayer; GlaxoSmithKline; Merck Sharp & Dohme LLC; Hoffmann-La Roche; AstraZeneca; Amgen; Sanofi Aventis GmbH, Austria; Wyeth Lederle Pharma GmbH, Austria; Fond of the Viennese Mayor
• Investigators: Study Director: Florian Fitzal, MD, Austrian Breast & Colorectal Cancer Study Group; Study Director: Michael Gnant, MD, Austrian Breast & Colorectal Cancer Study Group; Study Director: Guenther Steger, MD, Austrian Breast & Colorectal Cancer Study Group

Publications and helpful links

General Publications

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• Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. doi: 10.1056/NEJMoa003013.
• Babiera GV, Rao R, Feng L, Meric-Bernstam F, Kuerer HM, Singletary SE, Hunt KK, Ross MI, Gwyn KM, Feig BW, Ames FC, Hortobagyi GN. Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol. 2006 Jun;13(6):776-82. doi: 10.1245/ASO.2006.03.033. Epub 2006 Apr 17.
• Blanchard DK, Bhatia P, Hilsenbeck SG, Elledge RM. Does surgical management of stage IV breast cancer effect outcome? SABCC 2006, San Antonio
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• Yang YA, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, Patel SC, Khozin S, Liu ZY, Green J, Anver MR, Merlino G, Wakefield LM. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest. 2002 Jun;109(12):1607-15. doi: 10.1172/JCI15333.
• Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R. Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol. 2000 Apr;18(7):1423-31. doi: 10.1200/JCO.2000.18.7.1423.
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• Fitzal F, Sporn EP, Draxler W, Mittlbock M, Taucher S, Rudas M, Riedl O, Helbich TH, Jakesz R, Gnant M. Preoperative core needle biopsy does not increase local recurrence rate in breast cancer patients. Breast Cancer Res Treat. 2006 May;97(1):9-15. doi: 10.1007/s10549-005-6935-3.
• El-Tamer MB, Ward BM, Schifftner T, Neumayer L, Khuri S, Henderson W. Morbidity and mortality following breast cancer surgery in women: national benchmarks for standards of care. Ann Surg. 2007 May;245(5):665-71. doi: 10.1097/01.sla.0000245833.48399.9a.
• Bjelic-Radisic V, Fitzal F, Knauer M, Steger G, Egle D, Greil R, Schrenk P, Balic M, Singer C, Exner R, Soelkner L, Gnant M; ABCSG. Primary surgery versus no surgery in synchronous metastatic breast cancer: patient-reported quality-of-life outcomes of the prospective randomized multicenter ABCSG-28 Posytive Trial. BMC Cancer. 2020 May 6;20(1):392. doi: 10.1186/s12885-020-06894-2.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2010
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: November 17, 2009
• First Submitted That Met QC Criteria: November 17, 2009
• First Posted (Estimated): November 18, 2009

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; VEGF; circulating tumor cells; stem cells; growth factor; surgical therapy; ABCSG; POSYTIVE; median survival; surgery on demand; blood specimen; tissue specimen; TGF
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis; Neoplastic Cells, Circulating
• Other Study ID Numbers: ABCSG 28 / POSYTIVE; ABCSG 28 (Other Identifier: ABCSG)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO