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Breast CancerPhase 2Triple-BNCT01898117

Triple-B Study;Carboplatin-cyclophosphamide Versus Paclitaxel With or Without Atezolizumab as First-line Treatment in Advanced Triple Negative Breast Cancer

A Phase 2 study testing Carbo/cyclo, Carbo/cyclo + atezolizumab and Paclitaxel in people with Breast Cancer, run by The Netherlands Cancer Institute at 49 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Triple negative breast cancer (TNBC) is a difficult to treat molecular subtype with a poor survival. TNBC can be divided into at least two molecular entities; BRCA-like and non-BRCA-like. Read more about this study

Who is it for?
Any age
Conditions the study is for
Breast Cancer
What is being tested?
Carbo/cyclo, Carbo/cyclo + atezolizumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
304 participants
Where
49 sitesNetherlands
Study dates
Jul 2013to Dec 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Metastasized or locally advanced incurable triple negative breast cancer; patients with stage IV at diagnosis are eligible as well. If the primary lesion is the only measurable lesion according to RECIST criteria, every locoregional treatment must be mentioned to the investigators.
  • Histologically confirmed triple negative breast cancer (ER: < 10% nuclear staining of tumor cells on IHC; HER2: either score 0 or 1 at immunohistochemistry or negative at in situ hybridization [CISH or FISH] in case of score 2 or 3 on IHC)
  • Histological confirmation of triple negative breast cancer of a metastatic lesion is recommended
  • Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels
  • Primary tumor or metastasis tissue (10 x10 μm blank slides FFPE tumor material) sent to NKI-AVL for BRCA-like testing
  • Pretreatment histological biopsy of a metastatic lesion for the translational research questions (tumor tissue from bone metastases cannot be used).
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  • No previous cytotoxic therapy for metastatic disease
  • Disease-free interval of at least 12 months after completion of adjuvant paclitaxel or platinum compound therapy
  • Disease-free interval of at least 6 months after completion of adjuvant docetaxel
  • Measurable disease according to RECIST v1.1
  • WHO performance status of 0 or 1
  • Adequate bone marrow function: neutrophils ≥ 1.5 x 10E9 cells/l, platelets ≥100 x 10E9 cells/l, Hb ≥ 6.2 mmol/l.
  • Normal liver function: bilirubin < 1.5 x upper limit of the normal range (ULN); alkaline phosphatase < 2.5 x ULN (< 5 x ULN in case of liver metastases, and < 7 x ULN in case of bone metastases); transaminases (ASAT/ALAT) < 2.5 x ULN (and < 5 x ULN in case of liver metastases).
  • Normal renal function:
  • > calculated (Cockcroft-Gault) or measured creatinine clearance > 50 mL/min
  • INR < 1.5 and APTT normal, unless patient is on stable anti-coagulant treatment for at least two weeks with a low molecular weight heparin or coumarin, then an INR within the target range (usually between 2 and 3) is allowed.
  • Written informed consent

Who cannot join

  • Receptor conversion to hormone receptor positive (defined as >= 10% positive ER or PgR tumor cells) or HER2 positive
  • Another cancer except basal-cell carcinoma of the skin or in situ cervical cancer within the previous 5 years
  • Other antitumor therapy within the previous 21 days with the exception of endocrine therapy. The patient should have stopped any endocrine therapy before start study treatment.
  • Radiotherapy with palliative intent within the previous 7 days before randomization.
  • Known CNS disease except for treated brain metastases.
  • Uncontrolled serious medical or psychiatric illness
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  • Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03)) at inclusion
  • Severe infection within 4 weeks prior to randomization
  • received antibiotocs within 2 weeks prior to cycle 1, day 1
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgical procedure during the course of the study
  • New York Heart Association Class II or greater congestive heart failure. LVEF by MUGA, ultrasound or MRI must be ≥ 50% and should be performed within 4 weeks prior to randomization if cardiac failure is suspected.
  • History of myocardial infarction or unstable angina within 6 months prior to randomization
  • History of myocardial infarction or unstable angina or unstable arrhytmias within 3 months prior to randomization
  • futher criteria, see protocol

Trial locations and contacts

49 sites in 1 country.

49 sites in 1 country

Netherlands49 sites

  • MCA

    Alkmaar, 1815 JD

  • Noordwest Ziekenhuis Groep

    Alkmaar

  • ZGT

    Almelo, 7609 PP

  • Meander Medisch Centrum

    Amersfoort

  • BovenIJ

    Amsterdam, 1034 CS

  • Netherlands Cancer Institute

    Amsterdam, 1066 CX

  • AZVU

    Amsterdam, 1081 HV

  • OLVG

    Amsterdam

  • Gelre Ziekenhuis

    Apeldoorn

  • Rijnstate

    Arnhem

  • Lievensberg ziekenhuis

    Bergen op Zoom, 4624 VT

  • Rode Kruis Ziekenhuis

    Beverwijk, 1940 EB

  • Amphia

    Breda

  • IJsselland ziekenhuis

    Capelle aan den IJssel, 2906 ZC

  • Reinier de Graaf Gasthuis

    Delft

  • Deventer ziekenhuis

    Deventer, 7416 SE

  • Albert Schweitzer Ziekenhuis

    Dordrecht

  • Nijsmellinghe

    Drachten, 9202 NN

  • Ziekenhuis Gelderse Vallei

    Ede, 6716 RP

  • Maxima Medisch Centrum

    Eindhoven, 5631 BM

  • Catharina ziekenhuis

    Eindhoven

  • Jeroen Bosch ziekenhuis

    Eindhoven

  • Medisch Spectrum Twente (MST)

    Enschede

  • Admiraal de Ruyter ziekenhuis

    Goes

  • Groene Hart

    Gouda, 2803 HH

  • Groene Hart Ziekenhuis

    Gouda

  • Martini Ziekenhuis

    Groningen

  • St. Jansdal

    Harderwijk

  • Tergooi ziekenhuizen

    Hilversum

  • Spaarne Gasthuis

    Hoofddorp, 2134 TM

  • Dijklander ziekenhuis

    Hoorn

  • MCL

    Leeuwarden, 8934 AD

  • LUMC

    Leiden, 2333 ZA

  • Haaglanden MC

    Leidschendam, 2262 BA

  • MUMC

    Maastricht

  • St. Antonius ziekenhuis

    Nieuwegein

  • Bravis ziekenhuis

    Roosendaal

  • St. Fransicus Gasthuis

    Rotterdam, 3045 PM

  • Ikazia

    Rotterdam, 3083 AN

  • Maasstad Ziekenhuis

    Rotterdam

  • Stichting Franciscus Vlietland Groep locatie Gasthuis

    Rotterdam

  • Vlietland ziekenhuis

    Schiedam, 3118 JH

  • Zuyderland

    Sittard

  • Haga

    The Hague, 2545 CH

  • Elisabeth Tweesteden ziekenhuis

    Tilburg, 5042 AD

  • Diakonessenziekenhuis

    Utrecht

  • UMCU

    Utrecht

  • VieCuri Medisch Centrum voor Noord-Limburg

    Venlo

  • Isala Klinieken

    Zwolle, 8025 AB

Other trials in Netherlands

About this study

Official title: Biomarker Discovery Randomized Phase IIb Trial With Carboplatin-cyclophosphamide Versus Paclitaxel With or Without Atezolizumab as First-line Treatment in Advanced Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a difficult to treat molecular subtype with a poor survival. TNBC can be divided into at least two molecular entities; BRCA-like and non-BRCA-like. In this trial we would like to investigate whether a molecular subgroup exists within TNBCs that derives a benefit from atezolizumab added to first line chemotherapy.

Read the detailed description

Atezolizumab, a humanized monoclonal antibody that targets human programmed death-ligand 1 (PD-L1) has shown activity in TNBC. Early clinical trials with anti-PD-(L)1 monotherapy have shown that the median duration to response in TNBC is remarkably long (18 weeks) compared to cytotoxic chemotherapy. Since advanced TNBC is characterized by rapid disease progression, most patients with TNBC may not have the opportunity to derive benefit from immunotherapy. We hypothesize that by combining atezolizumab with paclitaxel or carboplatin-cyclophosphamide the desired rapid tumor control will be obtained with chemotherapy and subsequently atezolizumab can result in durable responses in a significant subset of patients. It is unknown whether addition of atezolizumab to first line chemotherapy in TNBC is more beneficial than adding this antibody to a second line treatment schedule. Because of this and because of the poor outcome of patients with advanced TNBC experiencing disease progression after first line palliative chemotherapy, patients who were randomized to a chemotherapy only arm in this study will be offered the opportunity to cross over to the other chemotherapy regimen plus atezolizumab at disease progression.

Conditions
Breast Cancer
Being tested
Carbo/cyclo, Carbo/cyclo + atezolizumab, Paclitaxel, Paclitaxel + Atezolizumab
Keywords
Triple negative, Metastatic
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carbo/cycloDrug

    Also called Carboplatin, Cyclophosphamide

  • Carbo/cyclo + atezolizumabDrug

    Also called Carboplatin, Cyclophosphamide, Atezolizumab

  • PaclitaxelDrug

  • Paclitaxel + AtezolizumabDrug

    Also called Paclitaxel, Atezolizumab

Study groups in NCT01898117
Study groupRoleWhat they receive
Carbo/cycloActive comparatorCarboplatin AUC=5 Cyclophosphamide 600 mg/m2 Q 4 weeks
Receives: Drug: Carbo/cyclo
Carbo/cyclo + AtezolizumabActive comparatorCarboplatin AUC=5 Cyclophosphamide 600 mg/m2 atezolizumab 840 mg d1,15 Q 4 weeks
Receives: Drug: Carbo/cyclo + atezolizumab
PaclitaxelActive comparatorPaclitaxel 90 mg/m2 d1, 8, 15 Q 4 weeks
Receives: Drug: Paclitaxel
Paclitaxel + atezolizumabActive comparatorPaclitaxel 90 mg/m2 d1, 8, 15 atezolizumab 840 mg d1,15 Q 4 weeks
Receives: Drug: Paclitaxel + Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Validate the BRCA1-like test

    Validate the BRCA1-like test in predicting differential PFS with first line alkylating and platinum agents (+/- antibody add-on) when compared to paclitaxel (+/- antibody add-on) in TNBC

    Measured: assessed up to 120 months

Secondary outcomes (20)

  1. Determine whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide for patients with PD-L1 positive tumors defined as combined positive score (CPS) 10 or higher (PFS1)

    Compare the overal survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and duration of response (DOR) between the groups

    Measured: Assessed up to 120 months

  2. Determine whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide (PFS1)

    Compare the overal survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and duration of response (DOR) between the groups

    Measured: Assessed up to 120 months

  3. Improvement of objective response by adding atezolizumab

    Determine whether atezolizumab added to first line palliative chemotherapy will result in more objective responses and a higher proportion of patients who are free of progression at 6 months and at 12 months

    Measured: assessed up to 120 months

  4. PD-L1 status (immunohistochemistry) in tumor infiltrating immune cells

    Analyze whether PD-L1 status (immunohistochemistry) in tumor infiltrating immune cells predicts for potential differential PFS benefit of atezolizumab added to first line palliative chemotherapy in TNBC

    Measured: Assessed up to 120 months

  5. Intratumoral CD8 and/or tumor-infiltrating lymphocytes (TIL)

    Analyze whether intratumoral CD8 and/or tumor-infiltrating lymphocytes (TIL) predict for differential PFS benefit of atezolizumab added to first line palliative chemotherapy in TNBC

    Measured: Assessed up to 120 months

  6. Compare PFS between alkylating-platinum regimen to paclitaxel as first line chemotherapy in BRCA1-like patients

    Evaluate whether an alkylating-platinum regimen is more effective than paclitaxel as first line chemotherapy regarding PFS in BRCA1-like TNBC

    Measured: Assessed up to 120 months

  7. Compare PFS between alkylating-platinum regimen to paclitaxel as first line chemotherapy in non BRCA1-like patients

    Evaluate whether an alkylating-platinum regimen is more effective than paclitaxel as first line chemotherapy regarding PFS in non BRCA1-like TNBC

    Measured: Assessed up to 120 months

  8. TNBC molecular subtypes- based on RNA -expression analysis

    define whether different TNBC molecular subtypes- based on RNA -expression analysis - predict for differential PFS benefit of atezolizumab added to first line palliative chemotherapy in TNBC

    Measured: Assessed up to 120 months

  9. pretreatment LDH level

    define whether pretreatment LDH level predicts for differential benefit of atezolizumab added to first line palliative chemotherapy in TNBC

    Measured: Assessed up to 120 months

  10. Define predictive biomarkers for objective response gain

    Define predictive biomarkers for objective response gain of the addition of atezolizumab to first line chemotherapy; e.g PD-L1, intratumoral CD8, TILs and pre-treatment LDH

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months

  11. Define predictive biomarkers for PFS gain- chemotherapy

    Define predictive biomarkers for PFS gain of carboplatin-cyclophosphamide or paclitaxel chemotherapy

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months

  12. Define predictive biomarkers for PFS gain - atezolizumab

    Define predictive biomarkers for PFS gain of addition of atezo lizumab to first line palliative chemotherapy in TNBC

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months

  13. Determine PFS in cross over

    Determine the PFS and objective response after cross over to the other chemotherapy regimen with atezolizumab (PFS2)

    Measured: At 6 and 12 months and up to 120 months

  14. Overal Response Rate (ORR)

    proportion of patients that is free of progression at 6 months and at 12 months after cross-over to the other chemotherapy regimen with atezolizumab

    Measured: Assessed up to 120 months

  15. Benefit Atezolizumab

    Evaluate whether addition of atezolizumab to chemotherapy in first line is more beneficial than when added in second line

    Measured: Assessed up to 120 months

  16. Overall survival (OS)

    Evaluation of overall survival (OS) for all (sub)group comparisons as pre-specified

    Measured: assessed up to 120 months

  17. Toxicity of all study regimens

    Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03

    Measured: Assessed at 1 year

  18. Efficay in patients treated with or without Bevacizumab

    Evaluate preliminary efficacy by PFS and OS in subgroups of patients treated before amendment 3 with carboplatin/cyclophosphamide or paclitaxel with or without bevacizumab

    Measured: Assessed up to 120 months

  19. Determine PFS in BRCA like TNBC

    Determine whether an alkylating platinum regimen is more effective then paclitaxel regarding PFS in BRCA like TNBC

    Measured: From date of randomization until date of first documented progression or date of death, which ever comes first, assessed up to 120 months

  20. putative predictive potential of BRCA1-like status

    Evaluate putative predictive potential of BRCA1-like status in various subgroups defined by treatment regimen received before amendment 3.

    Measured: Assessed up to 120 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2013 (estimated)
  2. Study startJul 2013
  3. Primary completion1 Apr 2024
  4. Study completionDec 2030 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
304 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01898117
Sponsor's protocol ID
M13TNB
Other IDs
2013-001484-23, NL44403.031.13
Acronym
Triple-B
Status last verified
Nov 2025
First submitted
27 Jun 2013
Last updated
26 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Egger SJ, Chan MMK, Luo Q, Wilcken N. Platinum-containing regimens for triple-negative metastatic breast cancer. Cochrane Database Syst Rev. 2020 Oct 21;10(10):CD013750. doi: 10.1002/14651858.CD013750.

    PubMed 33084020

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carbo/cyclo, Carbo/cyclo + atezolizumab and Paclitaxel in people with Breast Cancer, run by The Netherlands Cancer Institute at 49 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 17 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Validate the BRCA1-like test (time frame: assessed up to 120 months). 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 NCT01898117, 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 Nov 2025.

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