Systemic Therapy With or Without Upfront Surgery in Metastatic Breast Cancer (SUBMIT)

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Procedure: upfront breast surgery; Other: systemic therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upfront surgery; Upfront surgery followed by systemic treatment	Procedure: upfront breast surgery; surgery of primary tumor, lumpectomy or mastectomy
Other: Systemic therapy; Systemic therapy possibly followed by local treatment of the breast tumor	Other: systemic therapy; chemotherapy, immunotherapy or endocrine therapy (possibly followed by local surgery of the breast)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Two year survival	The percentage of patients who survive two years after randomization will be determined.	2 yrs after randomisation
Number of unplanned local therapies	The number of patients who will receive local treatment at another point than scheduled	5-6 months after randomisation
Difference in systemic therapy given	register which patients receive what treatments	6 months after randomisation
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
Number of treatments of the axillary lymph nodes	register which patients receive these treatments	6 months after randomisation

Collaborators and Investigators

• Sponsor: Jeroen Bosch Ziekenhuis
• Collaborators: Borstkanker Onderzoek Groep; Comprehensive Cancer Centre The Netherlands
• Investigators: Principal Investigator: M.F. Ernst, dr, Jeroen Bosch ziekenhuis; Principal Investigator: A.C. Voogd, dr, Maastricht University Medical Centre; Principal Investigator: V.C.G. Tjan-Heijnen, Prof, dr, Maastricht University Medical Centre

Publications and helpful links

General Publications

• Ruiterkamp J, Voogd AC, Tjan-Heijnen VC, Bosscha K, van der Linden YM, Rutgers EJ, Boven E, van der Sangen MJ, Ernst MF; Dutch Breast Cancer Trialists' Group (BOOG). SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation. BMC Surg. 2012 Apr 2;12:5. doi: 10.1186/1471-2482-12-5.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: February 2, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: survival; systemic therapy; upfront surgery
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BOOG 2010-05