Clinical trial NCT01392586: Systemic Therapy With or Without Upfront Surgery in Metastatic Breast Cancer
Official title: Systemic Therapy With or Without Up Front Surgery of the Primary Tumor in Breast Cancer Patients With Distant Metastases at Initial presenTation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Keywords: survival
systemic therapy
upfront surgery
Lead sponsor: Jeroen Bosch Ziekenhuis
Sponsor class: OTHER
Collaborators: name: Borstkanker Onderzoek Groep
name: Comprehensive Cancer Centre The Netherlands
First posted: 2011-07-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Survival
timeFrame: participants will be followed until death (expected median survival 31 months for surgery group)
Secondary outcomes:
measure: Quality of Life
timeFrame: 5 years after randomisation
measure: Two year survival
timeFrame: 2 yrs after randomisation
measure: Number of unplanned local therapies
timeFrame: 5-6 months after randomisation
measure: Difference in systemic therapy given
timeFrame: 6 months after randomisation
measure: Determination of pathological resection margin
timeFrame: Pathological report approximately 1 day after surgery
measure: Number of treatments of the axillary lymph nodes
timeFrame: 6 months after randomisation
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Assen
country: Netherlands
facility: Wilhelmina Ziekenhuis
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis
city: Blaricum
country: Netherlands
facility: Tergooiziekenhuizen, loc Blaricum
city: Delft
country: Netherlands
facility: Reinier de Graaf
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis, Loc. Leijweg
city: Den Haag
country: Netherlands
facility: Ziekenhuis Bronovo
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Heerlen
country: Netherlands
facility: Atrium Medisch Centrum
city: Helmond
country: Netherlands
facility: Ziekenhuis Elkerliek, loc Helmond
city: Hengelo
country: Netherlands
facility: Ziekenhuisgroep Twente, Loc. SMT
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: Diaconessenhuis
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis, Loc. Nieuwegein
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Sittard
country: Netherlands
facility: Orbis Medisch Centrum
city: Tilburg
country: Netherlands
facility: St. Elisabeth Ziekenhuis
city: Venlo
country: Netherlands
facility: Viecuri Medisch Centrum, loc. St Maartens Gasthuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Jeroen Bosch Ziekenhuis
name: M.F. Ernst, dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Centre
name: A.C. Voogd, dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Centre
name: V.C.G. Tjan-Heijnen, Prof, dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.