Metastatic Breast CancerPhase 3SUBMITNCT01392586
Systemic Therapy With or Without Upfront Surgery in Metastatic Breast Cancer
A Phase 3 study testing upfront breast surgery and systemic therapy in people with Metastatic Breast Cancer, run by Jeroen Bosch Ziekenhuis at 26 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- upfront breast surgery and systemic therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 26 sitesNetherlands
- Study dates
- Feb 2012to Jan 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Co-morbidity of the patient should allow surgery / systemic therapy
- Age > 18 years
- Written informed consent
Who cannot join
- 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
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
Netherlands26 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Medisch Centrum Alkmaar
Alkmaar
Ziekenhuisgroep Twente
Almelo
Wilhelmina Ziekenhuis
Assen
Rode Kruis Ziekenhuis
Beverwijk
Tergooiziekenhuizen, loc Blaricum
Blaricum
Reinier de Graaf
Delft
Catharina Ziekenhuis
Eindhoven
Maxima Medisch Centrum
Eindhoven
Atrium Medisch Centrum
Heerlen
Ziekenhuis Elkerliek, loc Helmond
Helmond
Ziekenhuisgroep Twente, Loc. SMT
Hengelo
Spaarne Ziekenhuis
Hoofddorp
Medisch Centrum Leeuwarden
Leeuwarden
Diaconessenhuis
Leiden
Maastricht University Medical Center
Maastricht
St. Antonius Ziekenhuis, Loc. Nieuwegein
Nieuwegein
Canisius-Wilhelmina Ziekenhuis
Nijmegen
UMC St. Radboud
Nijmegen
Ikazia Ziekenhuis
Rotterdam
Orbis Medisch Centrum
Sittard
Haga Ziekenhuis, Loc. Leijweg
The Hague
Ziekenhuis Bronovo
The Hague
St. Elisabeth Ziekenhuis
Tilburg
Viecuri Medisch Centrum, loc. St Maartens Gasthuis
Venlo
Isala Klinieken
Zwolle
About this study
Official title: 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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- upfront breast surgery, systemic therapy
- Keywords
- survival, systemic therapy, upfront surgery
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
upfront breast surgeryProcedure or surgery
surgery of primary tumor, lumpectomy or mastectomy
systemic therapyOther
chemotherapy, immunotherapy or endocrine therapy (possibly followed by local surgery of the breast)
| Study group | Role | What they receive |
|---|---|---|
| Upfront surgery | Experimental | Upfront surgery followed by systemic treatment Receives: Procedure: upfront breast surgery |
| Systemic therapy | Other | Systemic therapy possibly followed by local treatment of the breast tumor Receives: Other: systemic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.
Measured: participants will be followed until death (expected median survival 31 months for surgery group)
Secondary outcomes (6)
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
Measured: 5 years after randomisation
Two year survival
The percentage of patients who survive two years after randomization will be determined.
Measured: 2 yrs after randomisation
Number of unplanned local therapies
The number of patients who will receive local treatment at another point than scheduled
Measured: 5-6 months after randomisation
Difference in systemic therapy given
register which patients receive what treatments
Measured: 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.
Measured: Pathological report approximately 1 day after surgery
Number of treatments of the axillary lymph nodes
register which patients receive these treatments
Measured: 6 months after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2011 (estimated)
- Study startFeb 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: due to low accrual rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeroen Bosch Ziekenhuis
- Sponsor type
- University, hospital or other
- Collaborators
- Borstkanker Onderzoek Groep, Comprehensive Cancer Centre The Netherlands
- Responsible party
- Principal investigator, M.F. Ernst, dr, Jeroen Bosch Ziekenhuis
- Investigators
- M.F. Ernst, dr, Principal investigator, Jeroen Bosch ZiekenhuisA.C. Voogd, dr, Principal investigator, Maastricht University Medical CentreV.C.G. Tjan-Heijnen, Prof, dr, Principal investigator, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01392586
- Sponsor's protocol ID
- BOOG 2010-05
- Acronym
- SUBMIT
- Status last verified
- Feb 2014
- First submitted
- 5 Jul 2011
- Last updated
- 4 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 22469291
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Therapy With or Without Up Front Surgery of the Primary Tumor in Breast Cancer Patients With Distant Metastases at Initial presenTation
- ClinicalTrials.gov ID
- NCT01392586
- Acronym / sponsor ID
- SUBMIT / BOOG 2010-05
- Conditions
- Metastatic Breast Cancer
- Keywords
- survival, systemic therapy, upfront surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to low accrual rate
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Jeroen Bosch ZiekenhuisUniversity, hospital or other
- Collaborators
- Borstkanker Onderzoek Groep, Comprehensive Cancer Centre The Netherlands
- Study start
- Feb 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 12 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Upfront surgery | Experimental | Procedure: upfront breast surgeryUpfront surgery followed by systemic treatment |
| Systemic therapy | Other | Other: systemic therapySystemic therapy possibly followed by local treatment of the breast tumor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| upfront breast surgerysurgery of primary tumor, lumpectomy or mastectomy | Procedure or surgery | Upfront surgery |
| systemic therapychemotherapy, immunotherapy or endocrine therapy (possibly followed by local surgery of the breast) | Other | Systemic therapy |
Primary outcome
Survival
Time frame: participants will be followed until death (expected median survival 31 months for surgery group)
Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.
6 secondary outcomes
Quality of Life
Time frame: 5 years after randomisation
Two year survival
Time frame: 2 yrs after randomisation
Number of unplanned local therapies
Time frame: 5-6 months after randomisation
Difference in systemic therapy given
Time frame: 6 months after randomisation
Determination of pathological resection margin
Time frame: Pathological report approximately 1 day after surgery
Number of treatments of the axillary lymph nodes
Time frame: 6 months after randomisation
Results and safety
The study was stopped early (reason given: due to low accrual rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2014.
- Derived from this study: PubMed 22469291Ruiterkamp 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M.F. Ernst, dr principal investigator
Jeroen Bosch Ziekenhuis
A.C. Voogd, dr principal investigator
Maastricht University Medical Centre
V.C.G. Tjan-Heijnen, Prof, dr principal investigator
Maastricht University Medical Centre
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing upfront breast surgery and systemic therapy in people with Metastatic Breast Cancer, run by Jeroen Bosch Ziekenhuis at 26 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: due to low accrual rate). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: participants will be followed until death (expected median survival 31 months for surgery group)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01392586, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2014.