POSYTIVE: Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer

Sponsor

Austrian Breast & Colorectal Cancer Study Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01015625

Collaborator

Bayer (Industry), Amgen (Industry), Hoffmann-La Roche (Industry), AstraZeneca (Industry), Sanofi Aventis GmbH, Austria (Other), Wyeth Lederle Pharma GmbH, Austria (Other), GlaxoSmithKline (Industry), Merck Sharp & Dohme LLC (Industry), Fond of the Viennese Mayor (Other)

254

Enrollment

Locations

Arms

146

Duration (Months)

18.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Synchronous Metastasized Breast Cancer Circulating Tumor Cells	Procedure: Surgery Procedure: Surgery on Demand	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

254 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Oct 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

to evaluate the median survival of patients with synchronous metastasized breast cancer and the primary tumor in place comparing arm A with local therapy to the primary tumor versus arm B without local therapy [time point at which 50% of all randomized patient died]

Secondary Outcome Measures

time to distant progression (TTPd) [Time to treatment change due to systemic progression]
time to local progression (TTPl) [Increase in size >25% of the primary tumor in arm B (no local therapy). Local recurrence in arm A (local therapy).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Guessing	Guessing	Burgenland	Austria	7540
2	Hospital Oberpullendorf	Oberpullendorf	Burgenland	Austria	7350
3	Ordination Dr. Wette	St. Veit a. d. Glan	Carinthia	Austria	9300
4	Gynaegological Medical University Graz	Graz	Styria	Austria	8036
5	Medical University Graz, Oncology	Graz	Styria	Austria	8036
6	Medical University of Innsbruck	Innsbruck	Tyrol	Austria	6020
7	Ordensklinikum Linz GmbH - BHS Linz, Coop. Study Group	Linz	Upper Austria	Austria	4010
8	Ordensklinikum Linz GmbH - Elisabethinen Linz	Linz	Upper Austria	Austria	4010
9	General Hospital Linz	Linz	Upper Austria	Austria	4020
10	Klinikum Wels-Grieskirchen GmbH	Wels	Upper Austria	Austria	4600
11	State Hospital Feldkirch	Feldkirch	Vorarlberg	Austria	6807
12	Paracelsus Medical University Salzburg-Oncology, Coop. Group	Salzburg		Austria	5020
13	Medical University of Vienna-General Hospital Vienna	Vienna		Austria	1090
14	Medical University of Vienna	Vienna		Austria	1090

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