Recruitment

Recruitment Status
Recruiting

Inclusion Criteria

Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels
WHO performance status of 0 or 1
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).
...
Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels
WHO performance status of 0 or 1
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).
Adequate bone marrow function: neutrophils ≥ 1.5 x 10E9 cells/l, platelets ≥100 x 10E9 cells/l, Hb ≥ 6.2 mmol/l.
Disease-free interval of at least 12 months after completion of adjuvant paclitaxel or platinum compound therapy
Measurable disease according to RECIST v1.1
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)
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.
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.
Disease-free interval of at least 6 months after completion of adjuvant docetaxel
No previous cytotoxic therapy for metastatic disease
Histological confirmation of triple negative breast cancer of a metastatic lesion is recommended
Primary tumor or metastasis tissue (10 x10 μm blank slides FFPE tumor material) sent to NKI-AVL for BRCA-like testing
Written informed consent
Pretreatment histological biopsy of a metastatic lesion for the translational research questions (tumor tissue from bone metastases cannot be used).

Exclusion Criteria

Severe infection within 4 weeks prior to randomization
Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03)) at inclusion
Known CNS disease except for treated brain metastases.
...
Severe infection within 4 weeks prior to randomization
Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03)) at inclusion
Known CNS disease except for treated brain metastases.
Other antitumor therapy within the previous 21 days
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.
Receptor conversion to hormone receptor positive (defined as >= 10% positive ER or PgR tumor cells) or HER2 positive
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
received antibiotocs within 2 weeks prior to cycle 1, day 1
History of myocardial infarction or unstable angina or unstable arrhytmias within 3 months prior to randomization
History of myocardial infarction or unstable angina within 6 months prior to randomization
Radiotherapy with palliative intent within the previous 7 days before randomization.
Uncontrolled serious medical or psychiatric illness
Another cancer except basal-cell carcinoma of the skin or in situ cervical cancer within the previous 5 years

Summary

Conditions
Breast Cancer
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Factorial Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 125 years
Gender
Both males and females

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....

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.

Inclusion Criteria

Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels
WHO performance status of 0 or 1
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).
...
Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels
WHO performance status of 0 or 1
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).
Adequate bone marrow function: neutrophils ≥ 1.5 x 10E9 cells/l, platelets ≥100 x 10E9 cells/l, Hb ≥ 6.2 mmol/l.
Disease-free interval of at least 12 months after completion of adjuvant paclitaxel or platinum compound therapy
Measurable disease according to RECIST v1.1
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)
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.
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.
Disease-free interval of at least 6 months after completion of adjuvant docetaxel
No previous cytotoxic therapy for metastatic disease
Histological confirmation of triple negative breast cancer of a metastatic lesion is recommended
Primary tumor or metastasis tissue (10 x10 μm blank slides FFPE tumor material) sent to NKI-AVL for BRCA-like testing
Written informed consent
Pretreatment histological biopsy of a metastatic lesion for the translational research questions (tumor tissue from bone metastases cannot be used).

Exclusion Criteria

Severe infection within 4 weeks prior to randomization
Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03)) at inclusion
Known CNS disease except for treated brain metastases.
...
Severe infection within 4 weeks prior to randomization
Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03)) at inclusion
Known CNS disease except for treated brain metastases.
Other antitumor therapy within the previous 21 days
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.
Receptor conversion to hormone receptor positive (defined as >= 10% positive ER or PgR tumor cells) or HER2 positive
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
received antibiotocs within 2 weeks prior to cycle 1, day 1
History of myocardial infarction or unstable angina or unstable arrhytmias within 3 months prior to randomization
History of myocardial infarction or unstable angina within 6 months prior to randomization
Radiotherapy with palliative intent within the previous 7 days before randomization.
Uncontrolled serious medical or psychiatric illness
Another cancer except basal-cell carcinoma of the skin or in situ cervical cancer within the previous 5 years

Tracking Information

NCT #
NCT01898117
Collaborators
  • Borstkanker Onderzoek Groep
  • Roche Pharma AG
Investigators
  • Principal Investigator: Rianne Oosterkamp, MD MC Haaglanden Principal Investigator: Marleen Kok, MD NKI-AvL
  • Rianne Oosterkamp, MD MC Haaglanden Principal Investigator: Marleen Kok, MD NKI-AvL
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