Breast CancerPhase 3NNBC3-EuropeNCT01222052
6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients
A Phase 3 study testing 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel in people with Breast Cancer, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.
Trial summary
In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,150 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2002to Feb 2019
- 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 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological proven primary breast cancer
- Tumour size >0.5 cm and <5 cm (pT1b-pT2, pN0, M0)
- Axillary lymph nodes tumour free (node-negative disease)
- Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre
- Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision.
- Paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review.
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- HER-2/neu determination by immunohistochemistry. Patients will be stratified to be HER-2/neu-negative or HER-2/neu-positive (HER-2/neu Score 3+, or HER-2/neu Score 2+ and FISH positive).
- No distant metastasis
- Age >18 years, <70 years
- Performance status ECOG <2 (WHO Performance Status 0-1)
- Adequate cardiac function (echocardiographically measured left ventricular ejection fraction (LVEF) or shortening fraction (SF) within the normal limits, i.e. ≥55%)
- Adequate bone function (neutrophil count >1.5 x109 /l and platelet count >100 x109 /l)
- Adequate renal function (serum creatinine <120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin <1 x UNL, ASAT or ALAT (SGOT or SGPT) <2,5 x UNL)
- Before patient registration/randomization, written informed consent must be obtained according to ICH/EU GCP, and national/local regulations
Who cannot join
- Chemotherapy contraindicated
- Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node.
- Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel
- Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
- Estimated life-expectancy <10 years (irrespective of breast cancer diagnosis)
- Patient not accessible for treatment and follow up
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- Endocrine treatment not according to the latest standard recommendations of the AGO Kommission "Mamma"
- Pregnancy, lactation (sufficient non-hormonal contraception in fertile women required)
- Surgery more than six weeks ago at the start of chemotherapy
- Pre-existing polyneuropathy
- Previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- Prior chemotherapy or radiotherapy or endocrine therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Multicenter Study Comparing 6xFEC With 3xFEC-3xDoc in High-risk Node-negative Patients With Operable Breast Cancer: Comparison of Efficacy and Evaluation of Clinico-pathological and Biochemical Markers as Risk Selection Criteria
In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Due to their high prognostic impact, the tumour-biological invasion markers uPA/PAI-1 (urokinase-type plasminogen activator and its inhibitor PAI-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. This study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. The second study question refers to the comparison between an adjuvant combination treatment with FE100C*6 and a sequential treatment with FE100C*3 and Docetaxel*3.
Read the detailed description
- To compare FEC*6 with FEC*3 followed by DOC*3 with regard to:
- the primary endpoint of the study: Disease-Free Survival (DFS)
- the secondary endpoints: Overall Survival (OS), compliance, and toxicity of chemotherapy in each patient group
- To compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to:
- the proportion of low risk versus high risk patients
- DFS
- OS (secondary endpoint)
- Conditions
- Breast Cancer
- Being tested
- 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel
- Keywords
- high risk breast cancer, low risk breast cancer, uPA, urokinase-type plasminogen activator, PAI, plasminogen activator inhibitor-type
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-Fluorouracil, Epirubicin, Cyclophosphamide, DocetaxelDrug
Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks
Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A Taxane-containing | Experimental | 3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks Receives: Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel |
| Arm B standard anthracyclin | Active comparator | 6 courses of FEC q3weeks Receives: Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel |
| Observation | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival
Measured: after 10 years follow up
Secondary outcomes (1)
Overall Survival
Measured: after 10 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startJan 2002
- Primary completionFeb 2009
- Study completionFeb 2019 (estimated)
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 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
- 4,150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin-Luther-Universität Halle-Wittenberg
- Sponsor type
- University, hospital or other
- Collaborators
- GBG Forschungs GmbH
- Responsible party
- Principal investigator, Christoph Thomssen, Martin-Luther-Universität Halle-Wittenberg
- Investigators
- Christoph Thomssen, MD, Principal investigator, Dpt. Gynecology University Halle GermanyNadia Harbeck, MD, Principal investigator, Breast Center University Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222052
- Sponsor's protocol ID
- GBG 42
- Acronym
- NNBC3-Europe
- Status last verified
- Jun 2017
- First submitted
- 15 Oct 2010
- Last updated
- 26 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kantelhardt EJ, Vetter M, Schmidt M, Veyret C, Augustin D, Hanf V, Meisner C, Paepke D, Schmitt M, Sweep F, von Minckwitz G, Martin PM, Jaenicke F, Thomssen C, Harbeck N. Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6xFEC versus 3xFEC/3xDocetaxel. BMC Cancer. 2011 Apr 16;11:140. doi: 10.1186/1471-2407-11-140.
PubMed 21496284
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Multicenter Study Comparing 6xFEC With 3xFEC-3xDoc in High-risk Node-negative Patients With Operable Breast Cancer: Comparison of Efficacy and Evaluation of Clinico-pathological and Biochemical Markers as Risk Selection Criteria
- ClinicalTrials.gov ID
- NCT01222052
- Acronym / sponsor ID
- NNBC3-Europe / GBG 42
- Conditions
- Breast Cancer
- Keywords
- high risk breast cancer, low risk breast cancer, uPA, urokinase-type plasminogen activator, PAI, plasminogen activator inhibitor-type
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4,150 participants (actual)
- Lead sponsor
- Martin-Luther-Universität Halle-WittenbergUniversity, hospital or other
- Collaborators
- GBG Forschungs GmbH
- Study start
- Jan 2002
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2019 (estimated)
- First posted
- 18 Oct 2010 (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.
In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Due to their high prognostic impact, the tumour-biological invasion markers uPA/PAI-1 (urokinase-type plasminogen activator and its inhibitor PAI-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. This study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. The second study question refers to the comparison between an adjuvant combination treatment with FE100C*6 and a sequential treatment with FE100C*3 and Docetaxel*3.
Detailed description
- To compare FEC*6 with FEC*3 followed by DOC*3 with regard to:
- the primary endpoint of the study: Disease-Free Survival (DFS)
- the secondary endpoints: Overall Survival (OS), compliance, and toxicity of chemotherapy in each patient group
- To compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to:
- the proportion of low risk versus high risk patients
- DFS
- OS (secondary endpoint)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A Taxane-containing | Experimental | Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks |
| Arm B standard anthracyclin | Active comparator | Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel6 courses of FEC q3weeks |
| Observation | No intervention | – |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological proven primary breast cancer
- Tumour size >0.5 cm and <5 cm (pT1b-pT2, pN0, M0)
- Axillary lymph nodes tumour free (node-negative disease)
- Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre
- Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision.
Key exclusion criteria (12 listed)
- Chemotherapy contraindicated
- Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node.
- Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel
- Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
- Estimated life-expectancy <10 years (irrespective of breast cancer diagnosis)
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 |
|---|---|---|
| 5-Fluorouracil, Epirubicin, Cyclophosphamide, DocetaxelArm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks | Drug | Arm A Taxane-containing, Arm B standard anthracyclin |
Primary outcome
Disease-Free Survival
Time frame: after 10 years follow up
1 secondary outcome
Overall Survival
Time frame: after 10 years follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
- Derived from this study: PubMed 21496284Kantelhardt EJ, Vetter M, Schmidt M, Veyret C, Augustin D, Hanf V, Meisner C, Paepke D, Schmitt M, Sweep F, von Minckwitz G, Martin PM, Jaenicke F, Thomssen C, Harbeck N. Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6xFEC versus 3xFEC/3xDocetaxel. BMC Cancer. 2011 Apr 16;11:140. doi: 10.1186/1471-2407-11-140.
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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.
Christoph Thomssen, MD principal investigator
Dpt. Gynecology University Halle Germany
Nadia Harbeck, MD principal investigator
Breast Center University Cologne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel in people with Breast Cancer, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.
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 14 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
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?
Disease-Free Survival (time frame: after 10 years follow up). 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 NCT01222052, 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 26 Jun 2017.