Triple-B Study;Carboplatin-cyclophosphamide Versus Paclitaxel With or Without Atezolizumab as First-line Treatment in Advanced Triple Negative Breast Cancer
Triple-B
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
3 other identifiers
interventional
304
1 country
49
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started Jul 2013
Longer than P75 for phase_2 breast-cancer
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 27, 2013
CompletedStudy Start
First participant enrolled
July 1, 2013
CompletedFirst Posted
Study publicly available on registry
July 12, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
ExpectedNovember 26, 2025
November 1, 2025
10.8 years
June 27, 2013
November 21, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (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
assessed up to 120 months
Secondary Outcomes (20)
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)
Assessed up to 120 months
Determine whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide (PFS1)
Assessed up to 120 months
Improvement of objective response by adding atezolizumab
assessed up to 120 months
PD-L1 status (immunohistochemistry) in tumor infiltrating immune cells
Assessed up to 120 months
Intratumoral CD8 and/or tumor-infiltrating lymphocytes (TIL)
Assessed up to 120 months
- +15 more secondary outcomes
Study Arms (4)
Carbo/cyclo
ACTIVE COMPARATORCarboplatin AUC=5 Cyclophosphamide 600 mg/m2 Q 4 weeks
Carbo/cyclo + Atezolizumab
ACTIVE COMPARATORCarboplatin AUC=5 Cyclophosphamide 600 mg/m2 atezolizumab 840 mg d1,15 Q 4 weeks
Paclitaxel
ACTIVE COMPARATORPaclitaxel 90 mg/m2 d1, 8, 15 Q 4 weeks
Paclitaxel + atezolizumab
ACTIVE COMPARATORPaclitaxel 90 mg/m2 d1, 8, 15 atezolizumab 840 mg d1,15 Q 4 weeks
Interventions
Eligibility Criteria
You may qualify if:
- 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).
- 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
- +2 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Netherlands Cancer Institutelead
- Borstkanker Onderzoek Groepcollaborator
- Roche Pharma AGcollaborator
Study Sites (49)
MCA
Alkmaar, 1815 JD, Netherlands
Noordwest Ziekenhuis Groep
Alkmaar, Netherlands
ZGT
Almelo, 7609 PP, Netherlands
Meander Medisch Centrum
Amersfoort, Netherlands
BovenIJ
Amsterdam, 1034 CS, Netherlands
Netherlands Cancer Institute
Amsterdam, 1066 CX, Netherlands
AZVU
Amsterdam, 1081 HV, Netherlands
OLVG
Amsterdam, Netherlands
Gelre Ziekenhuis
Apeldoorn, Netherlands
Rijnstate
Arnhem, Netherlands
Lievensberg ziekenhuis
Bergen op Zoom, 4624 VT, Netherlands
Rode Kruis Ziekenhuis
Beverwijk, 1940 EB, Netherlands
Amphia
Breda, Netherlands
IJsselland ziekenhuis
Capelle aan den IJssel, 2906 ZC, Netherlands
Reinier de Graaf Gasthuis
Delft, Netherlands
Deventer ziekenhuis
Deventer, 7416 SE, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, Netherlands
Nijsmellinghe
Drachten, 9202 NN, Netherlands
Ziekenhuis Gelderse Vallei
Ede, 6716 RP, Netherlands
Maxima Medisch Centrum
Eindhoven, 5631 BM, Netherlands
Catharina ziekenhuis
Eindhoven, Netherlands
Jeroen Bosch ziekenhuis
Eindhoven, Netherlands
Medisch Spectrum Twente (MST)
Enschede, Netherlands
Admiraal de Ruyter ziekenhuis
Goes, Netherlands
Groene Hart
Gouda, 2803 HH, Netherlands
Groene Hart Ziekenhuis
Gouda, Netherlands
Martini Ziekenhuis
Groningen, Netherlands
St. Jansdal
Harderwijk, Netherlands
Tergooi ziekenhuizen
Hilversum, Netherlands
Spaarne Gasthuis
Hoofddorp, 2134 TM, Netherlands
Dijklander ziekenhuis
Hoorn, Netherlands
MCL
Leeuwarden, 8934 AD, Netherlands
LUMC
Leiden, 2333 ZA, Netherlands
Haaglanden MC
Leidschendam, 2262 BA, Netherlands
MUMC
Maastricht, Netherlands
St. Antonius ziekenhuis
Nieuwegein, Netherlands
Bravis ziekenhuis
Roosendaal, Netherlands
St. Fransicus Gasthuis
Rotterdam, 3045 PM, Netherlands
Ikazia
Rotterdam, 3083 AN, Netherlands
Maasstad Ziekenhuis
Rotterdam, Netherlands
Stichting Franciscus Vlietland Groep locatie Gasthuis
Rotterdam, Netherlands
Vlietland ziekenhuis
Schiedam, 3118 JH, Netherlands
Zuyderland
Sittard, Netherlands
Haga
The Hague, 2545 CH, Netherlands
Elisabeth Tweesteden ziekenhuis
Tilburg, 5042 AD, Netherlands
Diakonessenziekenhuis
Utrecht, Netherlands
UMCU
Utrecht, Netherlands
VieCuri Medisch Centrum voor Noord-Limburg
Venlo, Netherlands
Isala Klinieken
Zwolle, 8025 AB, Netherlands
Related Publications (1)
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.
PMID: 33084020DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rianne Oosterkamp, MD
MC Haaglanden
- PRINCIPAL INVESTIGATOR
Marleen Kok, MD
NKI-AvL
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 27, 2013
First Posted
July 12, 2013
Study Start
July 1, 2013
Primary Completion
April 1, 2024
Study Completion (Estimated)
December 1, 2030
Last Updated
November 26, 2025
Record last verified: 2025-11