Systemic Therapy With or Without Upfront Surgery in Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— SUBMIT  

Official title:

Systemic Therapy With or Without Up Front Surgery of the Primary Tumor in Breast Cancer Patients With Distant Metastases at Initial presenTation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01392586
• Other study ID #: BOOG 2010-05
• Status: Terminated
• Phase: Phase 3
• First received: July 5, 2011
• Last updated: February 2, 2014
• Start date: February 2012
• Est. completion date: January 2014

Study information

• Verified date: February 2014
• Source: Jeroen Bosch Ziekenhuis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

SUBMIT is a clinical trial that intends to answer the question whether up front breast surgery in patients with primary distant metastatic breast cancer will result in an improvement of the 2-year survival compared to the survival achieved with systemic therapy and delayed local treatment or systemic therapy alone.

Randomization will take place immediately after the diagnosis of primary distant metastatic breast cancer. Patients either randomize for up front surgery of the breast tumor (UFS) followed by systemic therapy or for systemic therapy (ST) potentially followed by delayed local treatment of the breast tumor.

The primary endpoint of this trial is the 2-years survival. Quality of life is one of the most important secondary endpoints.

Description:

In the Netherlands approximately one out of eight women will be diagnosed with breast cancer; 5% have metastatic disease at presentation. Because metastatic breast cancer is considered to be an incurable disease, it is only treated with a palliative intent. Recent retrospective studies have demonstrated that (complete) resection of the primary tumor significantly improves the outcome of patients with primary metastatic breast cancer. However, other studies showed that the survival benefit in patients who underwent surgery is caused by selection bias.

SUBMIT is a clinical trial that intends to answer the question whether up front breast surgery in patients with primary distant metastatic breast cancer will result in an improvement of the 2-year survival compared to the survival achieved with systemic therapy and delayed local treatment or systemic therapy alone.

Patients to submit in this study are patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy. Exclusion criteria are: history of breast cancer, other malignancy within the last 10 years, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor or synchronous bilateral breastcancer.

Randomization will take place immediately after the diagnosis of primary distant metastatic breast cancer. Patients either randomize for up front surgery of the breast tumor (UFS) followed by systemic therapy or for systemic therapy (ST) potentially followed by delayed local treatment of the breast tumor.

The primary endpoint of this trial is the 2-years survival. Quality of life is one of the most important secondary endpoints.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly diagnosed primary distant metastatic breast cancer (M1)

• Anticipated survival of at least 6 months

• Histologically proven breast cancer

• Hormonal and HER2Neu status should be known

• T1-T3, resectable T4 status, N0-N3

• Performance status of the patient should allow surgery / systemic therapy

• Co-morbidity of the patient should allow surgery / systemic therapy

• Age > 18 years

• Written informed consent

Exclusion Criteria:

• Primary invasive breast cancer in medical history

• Other malignancy within the last 10 years, besides basal cell carcinoma of the skin or early stage cervical cancer

• Surgical treatment / radiotherapy of this breast tumor before randomization

• Irresectable T4 breast tumor

• Synchronous bilateral breast cancer

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Procedure:
• upfront breast surgery
surgery of primary tumor, lumpectomy or mastectomy

Other:
• systemic therapy
chemotherapy, immunotherapy or endocrine therapy (possibly followed by local surgery of the breast)

Locations

Country	Name	City	State
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Ziekenhuisgroep Twente	Almelo
Netherlands	Wilhelmina Ziekenhuis	Assen
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	Tergooiziekenhuizen, loc Blaricum	Blaricum
Netherlands	Reinier de Graaf	Delft
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Haga Ziekenhuis, Loc. Leijweg	Den Haag
Netherlands	Ziekenhuis Bronovo	Den Haag
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	Atrium Medisch Centrum	Heerlen
Netherlands	Ziekenhuis Elkerliek, loc Helmond	Helmond
Netherlands	Ziekenhuisgroep Twente, Loc. SMT	Hengelo
Netherlands	Spaarne Ziekenhuis	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Diaconessenhuis	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	St. Antonius Ziekenhuis, Loc. Nieuwegein	Nieuwegein
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	Orbis Medisch Centrum	Sittard
Netherlands	St. Elisabeth Ziekenhuis	Tilburg
Netherlands	Viecuri Medisch Centrum, loc. St Maartens Gasthuis	Venlo
Netherlands	Isala Klinieken	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Jeroen Bosch Ziekenhuis	Borstkanker Onderzoek Groep, Comprehensive Cancer Centre The Netherlands

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.	participants will be followed until death (expected median survival 31 months for surgery group)	No
Secondary	Quality of Life	The EORTC QLQ - C30 and BR23 questionnaires will be used for the measurement of the quality of life. The quality of life will be assessed at 3, 6, 12, 18 months and 2,3,4,5 years after randomisation	5 years after randomisation	No
Secondary	Two year survival	The percentage of patients who survive two years after randomization will be determined.	2 yrs after randomisation	No
Secondary	Number of unplanned local therapies	The number of patients who will receive local treatment at another point than scheduled	5-6 months after randomisation	No
Secondary	Difference in systemic therapy given	register which patients receive what treatments	6 months after randomisation	No
Secondary	Determination of pathological resection margin	The definition of a complete resection in this trial means free resection margins for the invasive component.	Pathological report approximately 1 day after surgery	No
Secondary	Number of treatments of the axillary lymph nodes	register which patients receive these treatments	6 months after randomisation	No