Clinical Trials List
Protocol NumberWO29522
NCT Number(ClinicalTrials.gov Identfier)NCT02425891
2016-02-21 - 2020-12-31
Phase III
Not yet recruiting1
Terminated3
ICD-10C50
Malignant neoplasm of breast
A PHASE III, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY) IN COMBINATION WITH NAB-PACLITAXEL COMPARED WITH PLACEBO WITH NAB-PACLITAXEL FOR PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC TRIPLE NEGATIVE BREAST CANCER
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Trial Applicant
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Sponsor
F. Hoffmann-La Roche Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yao-Chung Wu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Liang-Chih Liu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Yi-Fang Tsai Division of General Surgery
- 邱仁輝 Division of General Surgery
- 金光亮 Division of General Surgery
- Chun-Yu Liu Division of Radiation Therapy
- Ta-Chung Chao Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 羅喬 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- 楊雅雯 Division of General Surgery
- Wei-Wu Chen Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- 郭文宏 Division of General Surgery
- 蔡立威 Division of General Surgery
- 林柏翰 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Audit
None
Co-Principal Investigator
- Fang-Ming Chen Division of Gastroenterological Surgery
- 甘蓉瑜 Division of Gastroenterological Surgery
- Chieh-Han Chuang Division of Gastroenterological Surgery
- Fu Ouyang Division of Gastroenterological Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Triple Negative Breast Cancer (TNBC)
Objectives
This multicenter, randomized, double-blind study evaluated the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.
Test Drug
Atezolizumab
Active Ingredient
Atezolizumab
Dosage Form
Vial
Dosage
1200mg/20ml
Endpoints
Primary Outcome Measures :
1. Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
2. PFS According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Baseline up to approximately 34 months ]
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
3. Overall Survival (OS) in All Randomized Participants [ Time Frame: Baseline until death due to any cause (up to approximately 58 months) ]
OS was defined as the time from the date of randomization to the date of death from any cause.
4. OS in Participants With Detectable PD-L1 [ Time Frame: Baseline until death due to any cause (up to approximately 58 months) ]
OS was defined as the time from the date of randomization to the date of death from any cause.
Secondary Outcome Measures :
1. Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
2. Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 34 months ]
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
3. Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
4. DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 34 months ]
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
5. Time to Deterioration (TTD) in Global Health Status/Health Related Quality of Life According to European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) v3.0 in All Randomized Participants [ Time Frame: Baseline up to approximately 58 months ]
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participant's GHS/HRQoL scale score showed a >=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of >= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of >= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
6. TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 58 months ]
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participants's GHS/HRQoL scale score showed a >=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of >= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of >= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
7. Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to 53 months ]
8. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline up to approximately 53 months ]
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
9. Maximum Serum Concentration (Cmax) for Atezolizumab [ Time Frame: Cycle 1 Day 1 (Cycle = 28 days) ]
Maximum serum concentration for atezolizumab.
10. Minimum Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days) ]
Minimum serum concentration for atezolizumab.
11. Plasma Concentrations of Total Paclitaxel [ Time Frame: Pre-dose (Hour 0) on Cycle 1 Day 1, pre-dose (Hour 0), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after end of nab-paclitaxel infusion (infusion duration = 30 minutes) on Cycle 3 Day 1 (Cycle = 28 days) ]
Plasma Concentrations of Total Paclitaxel
1. Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
2. PFS According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Baseline up to approximately 34 months ]
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
3. Overall Survival (OS) in All Randomized Participants [ Time Frame: Baseline until death due to any cause (up to approximately 58 months) ]
OS was defined as the time from the date of randomization to the date of death from any cause.
4. OS in Participants With Detectable PD-L1 [ Time Frame: Baseline until death due to any cause (up to approximately 58 months) ]
OS was defined as the time from the date of randomization to the date of death from any cause.
Secondary Outcome Measures :
1. Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
2. Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 34 months ]
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
3. Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants [ Time Frame: Baseline up to approximately 34 months ]
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
4. DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 34 months ]
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
5. Time to Deterioration (TTD) in Global Health Status/Health Related Quality of Life According to European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) v3.0 in All Randomized Participants [ Time Frame: Baseline up to approximately 58 months ]
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participant's GHS/HRQoL scale score showed a >=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of >= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of >= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
6. TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1 [ Time Frame: Baseline up to approximately 58 months ]
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participants's GHS/HRQoL scale score showed a >=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of >= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of >= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
7. Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to 53 months ]
8. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline up to approximately 53 months ]
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
9. Maximum Serum Concentration (Cmax) for Atezolizumab [ Time Frame: Cycle 1 Day 1 (Cycle = 28 days) ]
Maximum serum concentration for atezolizumab.
10. Minimum Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days) ]
Minimum serum concentration for atezolizumab.
11. Plasma Concentrations of Total Paclitaxel [ Time Frame: Pre-dose (Hour 0) on Cycle 1 Day 1, pre-dose (Hour 0), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after end of nab-paclitaxel infusion (infusion duration = 30 minutes) on Cycle 3 Day 1 (Cycle = 28 days) ]
Plasma Concentrations of Total Paclitaxel
Inclution Criteria
Inclusion Criteria:
• Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
• No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
• Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
• A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Measurable disease as defined by RECIST v1.1
• Adequate hematologic and end-organ function
• Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
• No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
• Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
• A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Measurable disease as defined by RECIST v1.1
• Adequate hematologic and end-organ function
Exclusion Criteria
Exclusion Criteria:
• Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
• Leptomeningeal disease
• Pregnancy or lactation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus
• Active hepatitis B or hepatitis C
• Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
• Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
• Leptomeningeal disease
• Pregnancy or lactation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus
• Active hepatitis B or hepatitis C
• Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
The Estimated Number of Participants
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Taiwan
18 participants
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Global
900 participants
