Triple-B Study;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.
Eligibility
Sex
ALL
Min age
—
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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
* 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
Exclusion Criteria:
* 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
* 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
Primary outcome measure(s)
Validate the BRCA1-like test — assessed up to 120 months 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
Trial sites (49)
Facility
City
Region
Status
MCA
Alkmaar
Netherlands
Noordwest Ziekenhuis Groep
Alkmaar
Netherlands
ZGT
Almelo
Netherlands
Meander Medisch Centrum
Amersfoort
Netherlands
BovenIJ
Amsterdam
Netherlands
Netherlands Cancer Institute
Amsterdam
Netherlands
AZVU
Amsterdam
Netherlands
OLVG
Amsterdam
Netherlands
Gelre Ziekenhuis
Apeldoorn
Netherlands
Rijnstate
Arnhem
Netherlands
Lievensberg ziekenhuis
Bergen op Zoom
Netherlands
Rode Kruis Ziekenhuis
Beverwijk
Netherlands
Amphia
Breda
Netherlands
IJsselland ziekenhuis
Capelle aan den IJssel
Netherlands
Reinier de Graaf Gasthuis
Delft
Netherlands
Deventer ziekenhuis
Deventer
Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht
Netherlands
Nijsmellinghe
Drachten
Netherlands
Ziekenhuis Gelderse Vallei
Ede
Netherlands
Maxima Medisch Centrum
Eindhoven
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
Netherlands
Groene Hart Ziekenhuis
Gouda
Netherlands
Martini Ziekenhuis
Groningen
Netherlands
St. Jansdal
Harderwijk
Netherlands
Tergooi ziekenhuizen
Hilversum
Netherlands
Spaarne Gasthuis
Hoofddorp
Netherlands
Dijklander ziekenhuis
Hoorn
Netherlands
MCL
Leeuwarden
Netherlands
LUMC
Leiden
Netherlands
Haaglanden MC
Leidschendam
Netherlands
MUMC
Maastricht
Netherlands
St. Antonius ziekenhuis
Nieuwegein
Netherlands
Bravis ziekenhuis
Roosendaal
Netherlands
St. Fransicus Gasthuis
Rotterdam
Netherlands
Ikazia
Rotterdam
Netherlands
Maasstad Ziekenhuis
Rotterdam
Netherlands
+ 9 more sites — see the full list on the official registry below.
More The Netherlands Cancer Institute trials in the Netherlands
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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