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

NCT ID: NCT01898117

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2030-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carbo/cyclo

Carboplatin AUC=5 Cyclophosphamide 600 mg/m2 Q 4 weeks

Group Type: ACTIVE_COMPARATOR

Carbo/cyclo

Intervention Type: DRUG

Carbo/cyclo + Atezolizumab

Carboplatin AUC=5 Cyclophosphamide 600 mg/m2 atezolizumab 840 mg d1,15 Q 4 weeks

Group Type: ACTIVE_COMPARATOR

Carbo/cyclo + atezolizumab

Intervention Type: DRUG

Paclitaxel

Paclitaxel 90 mg/m2 d1, 8, 15 Q 4 weeks

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Paclitaxel + atezolizumab

Paclitaxel 90 mg/m2 d1, 8, 15 atezolizumab 840 mg d1,15 Q 4 weeks

Group Type: ACTIVE_COMPARATOR

Paclitaxel + Atezolizumab

Intervention Type: DRUG

Interventions

Carbo/cyclo

Intervention Type: DRUG

Carbo/cyclo + atezolizumab

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Paclitaxel + Atezolizumab

Intervention Type: DRUG

Other Intervention Names

Carboplatin; Cyclophosphamide; Carboplatin; Cyclophosphamide; Atezolizumab; Paclitaxel; Atezolizumab

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rianne Oosterkamp, MD

Role: PRINCIPAL_INVESTIGATOR

MC Haaglanden

Marleen Kok, MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Locations

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

Stichting Franciscus Vlietland Groep locatie Gasthuis

Rotterdam, , Netherlands

Vlietland ziekenhuis

Schiedam, , Netherlands

Zuyderland

Sittard, , Netherlands

Haga

The Hague, , Netherlands

Elisabeth Tweesteden ziekenhuis

Tilburg, , Netherlands

Diakonessenziekenhuis

Utrecht, , Netherlands

UMCU

Utrecht, , Netherlands

VieCuri Medisch Centrum voor Noord-Limburg

Venlo, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 33084020 (View on PubMed)

Other Identifiers

2013-001484-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL44403.031.13

Identifier Type: OTHER

Identifier Source: secondary_id

M13TNB

Identifier Type: -

Identifier Source: org_study_id