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

This study has been terminated.
(due to low accrual rate)
Sponsor:
Collaborators:
Borstkanker Onderzoek Groep
Comprehensive Cancer Centre The Netherlands
Information provided by (Responsible Party):
M.F. Ernst, dr, Jeroen Bosch Ziekenhuis
ClinicalTrials.gov Identifier:
NCT01392586
First received: July 5, 2011
Last updated: February 2, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Procedure: upfront breast surgery
Other: systemic therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Systemic Therapy With or Without Up Front Surgery of the Primary Tumor in Breast Cancer Patients With Distant Metastases at Initial presenTation

Resource links provided by NLM:


Further study details as provided by Jeroen Bosch Ziekenhuis:

Primary Outcome Measures:
  • Survival [ Time Frame: participants will be followed until death (expected median survival 31 months for surgery group) ] [ Designated as safety issue: No ]
    Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.


Secondary Outcome Measures:
  • Quality of Life [ Time Frame: 5 years after randomisation ] [ Designated as safety issue: No ]
    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

  • Two year survival [ Time Frame: 2 yrs after randomisation ] [ Designated as safety issue: No ]
    The percentage of patients who survive two years after randomization will be determined.

  • Number of unplanned local therapies [ Time Frame: 5-6 months after randomisation ] [ Designated as safety issue: No ]
    The number of patients who will receive local treatment at another point than scheduled

  • Difference in systemic therapy given [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]
    register which patients receive what treatments

  • Determination of pathological resection margin [ Time Frame: Pathological report approximately 1 day after surgery ] [ Designated as safety issue: No ]
    The definition of a complete resection in this trial means free resection margins for the invasive component.

  • Number of treatments of the axillary lymph nodes [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]
    register which patients receive these treatments


Enrollment: 10
Study Start Date: February 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Upfront surgery
Upfront surgery followed by systemic treatment
Procedure: upfront breast surgery
surgery of primary tumor, lumpectomy or mastectomy
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392586

Locations
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
UMC St. Radboud
Nijmegen, Netherlands
Canisius-Wilhelmina Ziekenhuis
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, Netherlands
Sponsors and Collaborators
Jeroen Bosch Ziekenhuis
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
  More Information

No publications provided by Jeroen Bosch Ziekenhuis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.F. Ernst, dr, Dr.M.F.Ernst, Jeroen Bosch Ziekenhuis
ClinicalTrials.gov Identifier: NCT01392586     History of Changes
Other Study ID Numbers: BOOG 2010-05
Study First Received: July 5, 2011
Last Updated: February 2, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Jeroen Bosch Ziekenhuis:
survival
systemic therapy
upfront surgery

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 19, 2014