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Trial record 1 of 1 for:    NCT01898117
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Triple-B Study;Carboplatin-cyclophosphamide Versus Paclitaxel With or Without Atezolizumab as First-line Treatment in Advanced Triple Negative Breast Cancer (Triple-B)

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ClinicalTrials.gov Identifier: NCT01898117
Recruitment Status : Recruiting
First Posted : July 12, 2013
Last Update Posted : March 22, 2022
Sponsor:
Collaborators:
Borstkanker Onderzoek Groep
Roche Pharma AG
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Carbo/cyclo Drug: Carbo/cyclo + atezolizumab Drug: Paclitaxel Drug: Paclitaxel + Atezolizumab Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 304 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 2013
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Carbo/cyclo
Carboplatin AUC=5 Cyclophosphamide 600 mg/m2 Q 4 weeks
 Drug: Carbo/cyclo
Other Names:
  • Carboplatin
  • Cyclophosphamide
Active Comparator: Carbo/cyclo + Atezolizumab
Carboplatin AUC=5 Cyclophosphamide 600 mg/m2 atezolizumab 840 mg d1,15 Q 4 weeks
 Drug: Carbo/cyclo + atezolizumab
Other Names:
  • Carboplatin
  • Cyclophosphamide
  • Atezolizumab
Active Comparator: Paclitaxel
Paclitaxel 90 mg/m2 d1, 8, 15 Q 4 weeks
 Drug: Paclitaxel
Active Comparator: Paclitaxel + atezolizumab
Paclitaxel 90 mg/m2 d1, 8, 15 atezolizumab 840 mg d1,15 Q 4 weeks
 Drug: Paclitaxel + Atezolizumab
Other Names:
  • Paclitaxel
  • Atezolizumab


Outcome Measures
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Primary Outcome Measures :
  1. Validate the BRCA-like test [ Time Frame: assessed up to 120 months ]
    Validate the BRCA-like test in predicting differential PFS with first line alkylating and platinum agents when compared to paclitaxel in TNBC


Secondary Outcome Measures :
  1. Improvement of objective response by adding atezolizumab [ Time Frame: assessed up to 120 months ]
    Determine whether atezolizumab added to first line palliative chemotherapy improves objective response in TNBC

  2. Define predictive biomarkers for objective response gain [ Time Frame: 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 ]
    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

  3. Define predictive biomarkers for PFS gain [ Time Frame: 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 ]
    Define predictive biomarkers for PFS gain of carboplatin-cyclophosphamide or paclitaxel chemotherapy

  4. Determine PFS in BRCA like TNBC [ Time Frame: From date of randomization until date of first documented progression or date of death, which ever comes first, assessed up to 120 months ]
    Determine whether an alkylating platinum regimen is more effective then paclitaxel regarding PFS in BRCA like TNBC

  5. Determine PFS in non BRCA like TNBC [ Time Frame: From date of randomization until date of first documented progression or date of death, which ever comes first, assessed up to 120 months ]
    Determine whether paclitaxel is more effective then an alkylating platinum regimen regarding PFS in non BRCA like TNBC

  6. Overall survival (OS) [ Time Frame: assessed up to 120 months ]
    Evaluation of overall survival (OS) for all (sub)group comparisons as pre-specified for PFS

  7. Toxicity of all study regimens [ Time Frame: Assessed at 1 year ]
    Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03

  8. Determine PFS in cross over [ Time Frame: At 6 and 12 months and up to 120 months ]
    Determine the PFS and objective response after cross over to the other chemotherapy regimen with atezolizumab

  9. Determine PFS in TNBC molecular subtypes [ Time Frame: Assessed up to 120 months ]
    Determine whether TNBC molecular subtypes as defined by gene expression are predictive for differential PFS benefit of atezolizumab added to first line chemotherapy


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01898117


Contacts
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Contact: Sabine C Linn, Prof. MD +3120512 ext 2951 s.linn@nki.nl
Contact: Ingrid A. Mandjes, MSc +3120512 ext 2880 i.mandjes@nki.nl

Locations
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Sponsors and Collaborators
The Netherlands Cancer Institute
Borstkanker Onderzoek Groep
Roche Pharma AG
Investigators
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Principal Investigator: Rianne Oosterkamp, MD MC Haaglanden
Principal Investigator: Marleen Kok, MD NKI-AvL
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01898117    
Other Study ID Numbers: M13TNB
2013-001484-23 ( EudraCT Number )
NL44403.031.13 ( Other Identifier: CCMO )
First Posted: July 12, 2013    Key Record Dates
Last Update Posted: March 22, 2022
Last Verified: March 2022
Keywords provided by The Netherlands Cancer Institute:
Triple negative
Metastatic
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists