Clinical trial • Phase II • Oncology

Bevacizumab for Triple-negative breast cancer | Metastatic breast cancer

Phase II trial of Bevacizumab for Triple-negative breast cancer | Metastatic breast cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Triple-negative breast cancer | Metastatic breast cancer
Trial Stage
Phase II
Drug Modality
Monoclonal antibody | Small molecule

Key dates

Initial CTIS Submission Date
16-10-2024
First CTIS Authorization Date
22-11-2024

Trial design

Randomised, paclitaxel — comparator (intravenous paclitaxel; product entry lists max 90 mg/m2). carboplatin + cyclophosphamide — comparator regimen (carboplatin up to 750 mg iv; cyclophosphamide up to 600 mg/m2 iv). atezolizumab (tecentriq) or bevacizumab (avastin) used as add-on in some arms (atezolizumab product entries: 840 mg and 1200 mg iv formulations; bevacizumab listed up to 10 mg/kg iv).-controlled, crossover Phase II trial in Netherlands.

Randomised
Yes
Comparator
Paclitaxel — comparator (intravenous paclitaxel; product entry lists max 90 mg/m2). Carboplatin + Cyclophosphamide — comparator regimen (carboplatin up to 750 mg IV; cyclophosphamide up to 600 mg/m2 IV). Atezolizumab (Tecentriq) or Bevacizumab (Avastin) used as add-on in some arms (atezolizumab product entries: 840 mg and 1200 mg IV formulations; bevacizumab listed up to 10 mg/kg IV).
Crossover
Yes
Biomarker Stratified
True, BRCA1-like status: BRCA1-like | non-BRCA1-like
Target Sample Size
306

Eligibility

Recruits 306 Vulnerable populations not selected (isVulnerablePopulationSelected: false). Consent/assent handling not specifically described in the available criteria documents..

Vulnerable Population
Vulnerable populations not selected (isVulnerablePopulationSelected: false). Consent/assent handling not specifically described in the available criteria documents.

Inclusion criteria

  • {"criterion_text":"- Histologically confirmed triple negative metastasized or locally advanced incurable breast cancer"}
  • {"criterion_text":"- WHO performance status of 0 or 1"}
  • {"criterion_text":"- Histological confirmation of triple negative breast cancer of a metastatic lesion is recommended"}
  • {"criterion_text":"- Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels"}
  • {"criterion_text":"- Primary tumor or metastasis tissue sent to NKI-AVL for BRCA1-like testing"}
  • {"criterion_text":"- Pretreatment histological biopsy of a metastatic lesion for the translational research questions (tumor tissue from bone metastases cannot be used)"}
  • {"criterion_text":"- No previous cytotoxic therapy for metastatic disease"}
  • {"criterion_text":"- Disease-free interval of at least 12 months after completion of (neo)adjuvant paclitaxel or (neo)adjuvant platinum compound"}
  • {"criterion_text":"- Disease-free interval of at least 6 months after completion of (neo) adjuvant docetaxel"}
  • {"criterion_text":"- Measurable or evaluable disease according to RECIST V1.1"}

Exclusion criteria

  • {"criterion_text":"- Receptor conversion to hormone receptor positive (defined as ≥ 10% ER positive tumor cells) or HER2 positive"}
  • {"criterion_text":"- Prior allogeneic stem cell or solid organ transplantation"}
  • {"criterion_text":"- History of lung diseases such as idiopathic pulmonary fibrosis, pneumonitis"}
  • {"criterion_text":"- An infection requiring parenteral antibiotic"}
  • {"criterion_text":"- Positive test for hepatitis B, C or HIV"}
  • {"criterion_text":"- Active tuberculosis"}
  • {"criterion_text":"- Live, attenuated vaccine within 4 weeks prior to randomization"}
  • {"criterion_text":"- Prior treatment with anti cancer vaccins or immune checkpoint blockade therapies, including anti-CTLA-4, CD137 agonist, OX40 agonist, anti-PD-1, or anti-PD-L1 therapeutic antibodies"}
  • {"criterion_text":"- Treatment with systemic immunostimulatory agents, systemic corticosteroids or other systemic immunosuppressive medications"}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Radiotherapy with palliative intent within the previous 7 days before start study medication"}
  • {"criterion_text":"- Known CNS disease except for treated brain metastases"}
  • {"criterion_text":"- Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03) at inclusion)"}
  • {"criterion_text":"- Use of denosumab is not allowed"}
  • {"criterion_text":"- Severe infection in the last 4 weeks"}
  • {"criterion_text":"- Antibiotics in the last 2 weeks"}
  • {"criterion_text":"- History of autoimmune disease"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Interaction test of BRCA1-like status vs. treatment (CC vs. paclitaxel (both arms with or without atezolizumab or bevacizumab (patients before amendment 3)) and PFS according to RECIST v1.1 definitions for measurable and non-measurable disease 1-3.","definition_or_measurement_approach":"Progression-free survival (PFS) according to RECIST v1.1 definitions for measurable and non-measurable disease; interaction test of BRCA1-like status versus treatment arms."}

Secondary endpoints

  • {"endpoint_text":"- Evaluate 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 CPS 10 or higher (PFS1)","definition_or_measurement_approach":"PFS1 comparison in PD-L1 CPS ≥10 subgroup"}
  • {"endpoint_text":"- Evaluate whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide (PFS1)","definition_or_measurement_approach":"PFS1 comparison between atezolizumab added to paclitaxel versus atezolizumab added to carboplatin-cyclophosphamide"}
  • {"endpoint_text":"- Test the benefit of the addition of atezolizumab to chemotherapy using objective response rate (ORR), proportion of patients free of progression at 6 months and at 12 months, all according to RECIST v1.1 definitions (see also appendix F) 1-3.","definition_or_measurement_approach":"ORR and proportion progression-free at 6 and 12 months measured per RECIST v1.1"}
  • {"endpoint_text":"- Overall- survival (OS) benefit of the addition of atezolizumab versus no atezolizumab to first line palliative chemotherapy. OS is measured from the day of randomization to the occurrence of death of any cause.","definition_or_measurement_approach":"OS measured from randomization to death from any cause"}
  • {"endpoint_text":"- Determine PFS and OS regarding the efficacy of the two different first line chemotherapeutic regimens, regardless of antibody add-on yes or no, in the whole study group, and in the BRCA1-like and non-BRCA1-like TNBC subgroups separately.","definition_or_measurement_approach":"PFS and OS comparisons overall and by BRCA1-like status"}
  • {"endpoint_text":"- Evaluate whether a PFS/ORR/OS difference exists between efficacy of atezolizumab added to chemotherapy in BRCA1-like TNBC and in non-BRCA1-like TNBC, regardless of chemotherapy regimen","definition_or_measurement_approach":"PFS/ORR/OS comparisons by BRCA1-like versus non-BRCA1-like status"}
  • {"endpoint_text":"- Evaluate whether a PFS/ORR/OS difference exists between efficacy of atezolizumab added to chemotherapy in BRCA1-like TNBC and non-BRCA1-like TNBC, stratified by chemotherapy regimen","definition_or_measurement_approach":"Stratified PFS/ORR/OS analyses by chemo regimen and BRCA1-like status"}
  • {"endpoint_text":"- Evaluate whether an alkylating-platinum regimen is more effective than paclitaxel as first line chemotherapy regarding PFS/OS in BRCA1-like TNBC","definition_or_measurement_approach":"PFS/OS comparison between alkylating-platinum regimen and paclitaxel in BRCA1-like subgroup"}
  • {"endpoint_text":"- Evaluate whether paclitaxel is more effective than an alkylating regimen as first line chemotherapy regarding PFS/OS in non-BRCA1-like TNBC","definition_or_measurement_approach":"PFS/OS comparison in non-BRCA1-like subgroup"}
  • {"endpoint_text":"- Define whether PD-L1 status predicts for benefit of atezolizumab added to first line palliative chemotherapy in TNBC; test association between PD-L1 status and ORR, proportion of patients free of progression at 6 months and at 12 months stratified by chemotherapy regimen","definition_or_measurement_approach":"Association tests between PD-L1 status and ORR/proportion progression-free at 6 and 12 months"}
  • {"endpoint_text":"- Define whether tumor intratumoral CD8 and tumor infiltrating lymphocytes (TIL) predicts for benefit of atezolizumab added to first line palliative chemotherapy in TNBC; test the association between intratumoral CD8 (cut off to be determined) and ORR, proportion of patients free at progression at 6 and 12 months stratified by chemotherapy regimen.","definition_or_measurement_approach":"Association analyses of intratumoral CD8/TIL with ORR and progression-free proportions at 6 and 12 months"}
  • {"endpoint_text":"- Determine whether certain molecular TNBC subtypes (based on RNA-expression analysis) are predictive for benefit of atezolizumab to first line chemotherapy using ORR, proportion of patients free of progression at 6 months and at 12 months","definition_or_measurement_approach":"Predictive analyses by RNA-expression defined TNBC subtypes using ORR and progression-free proportions"}
  • {"endpoint_text":"- Discovery of predictive biomarkers for benefit of atezolizumab added to first line palliative chemotherapy in TNBC using ORR, proportion of patients free of progression at 6 months and at 12 months","definition_or_measurement_approach":"Exploratory biomarker discovery using ORR and progression-free proportions"}
  • {"endpoint_text":"- To define whether pretreatment LDH level (cut off to be determined) predicts for benefit of atezolizumab added to first line palliative chemotherapy in TNBC using ORR, proportion of patients free of progression at 6 months and at 12 months","definition_or_measurement_approach":"Association of pretreatment LDH level with ORR and progression-free proportions"}
  • {"endpoint_text":"- Exploratory analysis to define biomarkers that can predict for a PFS/OS advantage of carboplatin-cyclophosphamide as first line palliative chemotherapy in TNBC","definition_or_measurement_approach":"Exploratory biomarker analyses for PFS/OS advantage with carboplatin-cyclophosphamide"}
  • {"endpoint_text":"- Exploratory analysis to define biomarkers that can predict for a PFS/OS advantage of paclitaxel as first line palliative chemotherapy in TNBC","definition_or_measurement_approach":"Exploratory biomarker analyses for PFS/OS advantage with paclitaxel"}
  • {"endpoint_text":"- Evaluation of progression free survival (PFS2)/ORR and proportion of patients free of progression at 6 months and 12 months after cross-over to the other chemotherapy regimen with atezolizumab","definition_or_measurement_approach":"PFS2/ORR and progression-free proportions at 6 and 12 months measured after crossover"}
  • {"endpoint_text":"- Evaluate whether addition of atezolizumab to chemotherapy in first line is more beneficial than when added in second line","definition_or_measurement_approach":"Comparative analyses of benefit of atezolizumab when added in first versus second line"}
  • {"endpoint_text":"- Clinically relevant toxicity of all study regimens according to NCI CTCAE v4.03","definition_or_measurement_approach":"Safety assessment using NCI CTCAE v4.03"}

Recruitment

Planned Sample Size
306
Recruitment Window Months
174
Consent Approach
Informed consent via subject information and informed consent form documents (L1_SIS and ICF general public; L1_SIS and ICF immunohub public, version 13.1). No further details on assent, age-specific consent processes, or available languages are provided in the available records.

Geography

Total Number Of Sites
34
Total Number Of Participants
306

Netherlands

Earliest CTIS Part Ii Submission Date
14-11-2024
Latest Decision Or Authorization Date
22-11-2024
Processing Time Days
8
Number Of Sites
34
Number Of Participants
306

Sites

Site Name
Zuyderland Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Franchette van den Berkmortel
Site Name
Catharina Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Birgit Vriens
Site Name
Albert Schweitzer Ziekenhuis
Department Name
Oncology
Contact Person Name
Jos Kitzen
Contact Person Email
j.j.e.m.kitzen@asz.nl
Site Name
Stichting Martini Ziekenhuis
Department Name
Internal medicine
Contact Person Name
Annette van der Velden
Contact Person Email
a.vandervelden@mzh.nl
Site Name
Diakonessenhuis Stichting
Department Name
Oncology
Contact Person Name
Lobke van Leeuwen
Contact Person Email
researchoncologie@diakhuis.nl
Site Name
Stichting Amsterdam UMC
Department Name
Medical Oncology
Contact Person Name
Inge Konings
Contact Person Email
medonc-mammae@amsterdamumc.nl
Site Name
Academisch Ziekenhuis Maastricht
Department Name
Medical Oncology
Contact Person Name
Maaike de Boer
Contact Person Email
maaike.deboer@mumc.nl
Site Name
Noordwest Ziekenhuisgroep Stichting
Department Name
Oncology
Contact Person Name
Suzan Vrijaldenhoven
Contact Person Email
trialbureauoncologie@nwz.nl
Site Name
Ziekenhuis St Jansdal
Department Name
Oncology
Contact Person Name
Asia Ropela
Contact Person Email
JA.Ropela@stjansdal.nl
Site Name
Stichting OLVG
Department Name
Internal medicine / Oncology
Contact Person Name
Emile Kerver
Site Name
Gelre Hospitals
Department Name
Internal medicine
Contact Person Name
Cathrien Tromp-van Driel
Contact Person Email
c.tromp@gelre.nl
Site Name
Amphia Hospital
Department Name
Oncology
Contact Person Name
Joan Heijns
Contact Person Email
JHeijns@amphia.nl
Site Name
Sint Franciscus Vlietland Groep Stichting
Department Name
Oncology
Contact Person Name
Hanneke Zuetenhorst
Contact Person Email
researchinterne@franciscus.nl
Site Name
Haga Hospital
Department Name
Internal medicine
Contact Person Name
Daniël Houtsma
Contact Person Email
d.houtsma@hagaziekenhuis.nl
Site Name
Sint Antonius Ziekenhuis Stichting
Department Name
Internal medicine / Oncology
Contact Person Name
Mariëtte Agterof
Site Name
Admiraal De Ruyter Ziekenhuis B.V.
Department Name
Internal medicine / Oncology
Contact Person Name
Henk van Halteren
Contact Person Email
hk.vanhalteren@adrz.nl
Site Name
Dijklander Ziekenhuis
Department Name
Oncology
Contact Person Name
Simone van den Heiligenberg
Site Name
Jeroen Bosch Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Jolien Tol
Contact Person Email
j.tol@jbz.nl
Site Name
Stichting Elisabeth-Tweesteden Ziekenhuis
Department Name
Trialoffice Oncology-Hematology
Contact Person Name
Anne-Marie van Riel
Contact Person Email
jmgh.vanriel@etz.nl
Site Name
Medisch Centrum Leeuwarden B.V.
Department Name
Oncology center Leeuwarden
Contact Person Name
Lisanne Hamming
Contact Person Email
lisanne.hamming@mcl.nl
Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Medical Oncology
Contact Person Name
Marleen Kok
Contact Person Email
m.kok@nki.nl
Site Name
Reinier de Graaf Groep
Department Name
Internal medicine / Oncology
Contact Person Name
Annelie Vulink
Contact Person Email
Balieoncohema@rdgg.nl
Site Name
Deventer Ziekenhuis
Department Name
Medical Oncology
Contact Person Name
Alex Imholz
Contact Person Email
imholza@dz.nl
Site Name
Ziekenhuis Gelderse Vallei Stichting
Department Name
Oncology center
Contact Person Name
Maartje Verstappen
Contact Person Email
verstappenm@zgv.nl
Site Name
Ziekenhuisgroep Twente Stichting
Department Name
Oncology center
Contact Person Name
Irma Oving
Contact Person Email
secretariaatintonc@zgt.nl
Site Name
Medisch Spectrum Twente
Department Name
Internal medicine
Contact Person Name
Marjolein Pleunis-van Empel
Contact Person Email
ResearchOC@mst.nl
Site Name
Bravis Ziekenhuis
Department Name
Oncology center
Contact Person Name
Frederiek Terheggen
Contact Person Email
f.terheggen@bravis.nl
Site Name
Maxima Medisch Centrum
Department Name
Oncology
Contact Person Name
Wouter Dercksen
Contact Person Email
secr.MOC@mmc.nl
Site Name
Stichting Viecuri Medisch Centrum voor Noord-Limburg
Department Name
Internal medicine / Oncology
Contact Person Name
Eline Boon
Contact Person Email
elineboon@viecuri.nl
Site Name
Meander Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Christa van Schaik-van de Mheen
Site Name
Rijnstate Ziekenhuis Stichting
Department Name
Oncology center
Contact Person Name
Rutger Koornstra
Contact Person Email
RCOO@Rijnstate.nl
Site Name
Spaarne Gasthuis Stichting
Department Name
Oncology-Hematology
Contact Person Name
Bart de Valk
Site Name
Groene Hart Ziekenhuis
Department Name
Internal medicine / Oncology
Contact Person Name
Wendy van der Deure
Contact Person Email
Wendy.van.der.deure@ghz.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Medical Oncology
Contact Person Name
Rhodé Bijlsma
Contact Person Email
oncostudies@umcutrecht.nl

Sponsor

Primary sponsor

Full Name
BOOG Study Center B.V.
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Netherlands

Third parties

  • {"country":"Netherlands","full_name":"Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting","duties_or_roles":"1|10|11|13|4|6|7|8","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Netherlands","full_name":"IKNL","duties_or_roles":"7","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Avastin 25 mg/ml concentrate for solution for infusion.
Active Substance
Bevacizumab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (prodAuthStatus: 2)
Maximum Dose
10 mg/kg
Investigational Product Name
CARBOPLATIN
Active Substance
Carboplatin
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (prodAuthStatus: 2, scientificProductEvCode: SCP10337134)
Maximum Dose
750 mg
Investigational Product Name
PACLITAXEL
Active Substance
Paclitaxel
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (prodAuthStatus: 2, scientificProductEvCode: SCP129816)
Maximum Dose
90 mg/m2
Investigational Product Name
Tecentriq 840 mg concentrate for solution for infusion / Tecentriq 1 200 mg concentrate for solution for infusion
Active Substance
Atezolizumab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (prodAuthStatus: 2)
Maximum Dose
840 mg or 1200 mg (formulation dependent)
Investigational Product Name
CYCLOPHOSPHAMIDE
Active Substance
Cyclophosphamide
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (prodAuthStatus: 2, scientificProductEvCode: SCP106382672)
Maximum Dose
600 mg/m2
Combination Treatment
Yes

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