Clinical Trials List
Protocol NumberWO39391
NCT Number(ClinicalTrials.gov Identfier)NCT03498716
2018-08-31 - 2026-05-31
Phase III
Not yet recruiting3
Recruiting1
Terminated9
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A PHASE III, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY COMPARING ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY) IN COMBINATION WITH ADJUVANT ANTHRACYCLINE/TAXANE-BASED CHEMOTHERAPY VERSUS CHEMOTHERAPY ALONE IN PATIENTS WITH OPERABLE TRIPLE-NEGATIVE BREAST CANCER
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
F. Hoffmann-La Roche Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of General Surgery
- 蔡立威 Division of General Surgery
- 楊雅雯 Division of General Surgery
- 林柏翰 Division of General Surgery
- 羅喬 Division of General Surgery
- Wei-Wu Chen Division of General Surgery
- 林季宏 Division of General Surgery
- 郭文宏 Division of General Surgery
- 張端瑩 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Ming-Hung Tsai Division of Hematology & Oncology
- Yao-Chung Wu Division of Hematology & Oncology
- Liang-Chih Liu Division of Hematology & Oncology
- HWEI-CHUNG WANG Division of Hematology & Oncology
- Chen-Teng Wu Division of Hematology & Oncology
- Chih-Jung Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Yi-Fang Tsai Division of General Surgery
- 賴亦貞 Division of General Surgery
- Ta-Chung Chao Division of General Surgery
- 林燕淑 Division of General Surgery
- 馮晉榮 Division of General Surgery
- 邱仁輝 Division of General Surgery
- Chun-Yu Liu Division of General Surgery
The Actual Total Number of Participants Enrolled
2 Not yet recruiting
Audit
None
Co-Principal Investigator
- Chi-Chang Yu Division of General Surgery
- Yung-Chang Lin Division of General Surgery
- Wen-Ling Kuo Division of General Surgery
- Mengting Peng Division of General Surgery
- 周旭桓 Division of General Surgery
- Wen-Chi Shen Division of General Surgery
- 沈士哲 Division of General Surgery
- Chia-Hui Chu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wu-Chou Su Division of Hematology & Oncology
- Kuo-Ting Lee Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Zhu-Jun Loh Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Yao-Lung Kuo Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 何景良 Division of General Surgery
- 吳宜穎 Division of General Surgery
- 廖國秀 Division of General Surgery
- 戴明燊 Division of General Surgery
- 陳佳宏 Division of General Surgery
- 陳宇欽 Division of General Surgery
- 黃子權 Division of General Surgery
- 洪志杰 Division of General Surgery
- 張平穎 Division of General Surgery
- 葉人華 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Fang-Ming Chen Division of General Surgery
- Junping Shiau Shiau 無
- 巫承哲 Division of General Surgery
- 高捷妮 無
- 甘蓉瑜 Division of General Surgery
- Chung-Liang Li 無
- Chieh-Han Chuang Division of General Surgery
- Shen Liang Shih 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 蔡郁棻 無
- 洪朝明 Division of General Surgery
- 李蕙鳴 無
- Meng-Jer Hsieh Division of General Surgery
- 裴松南 無
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Hong Cheng 無
- 洪進昇醫師 無
- 劉惠文醫師 無
- 莊博雅 無
- 譚家偉醫師 無
- Yao-Yu Hsieh 無
- 蘇智銘醫師 無
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Triple-Negative Breast Cancer
Objectives
Primary Efficacy Objective:
●To evaluate the efficacy of adjuvant atezolizumab + T-AC/EC compared with T AC/EC alone in patients with TNBC
Secondary Efficacy Objectives:
●To evaluate the efficacy of adjuvant atezolizumab + T-AC/EC compared with T AC/EC alone
●To evaluate PROs of function and HRQoL associated with atezolizumab + T-AC/EC compared with T AC/EC alone, as measured by the functional and HRQoL scales of the EORTC QLQ-C30
Test Drug
Atezolizumab (RO5541267)
Active Ingredient
Atezolizumab (RO5541267)
Dosage Form
Injection
Dosage
1200
Endpoints
iDFS, defined as the time from randomization until the date of the first occurrence of one of the following events:
- Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion)
- Ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast)
- Ipsilateral second primary invasive breast cancer
- Contralateral invasive breast cancer
- Distant recurrence (i.e., evidence of breast cancer in any anatomic site [other than the sites mentioned above]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer
- Death attributable to any cause, including breast cancer,non-breast cancer, or unknown cause
- Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion)
- Ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast)
- Ipsilateral second primary invasive breast cancer
- Contralateral invasive breast cancer
- Distant recurrence (i.e., evidence of breast cancer in any anatomic site [other than the sites mentioned above]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer
- Death attributable to any cause, including breast cancer,non-breast cancer, or unknown cause
Inclution Criteria
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form (ICF)
• Ability to comply with protocol, in the investigator’s judgment
• Women or men aged ≥ 18 years at time of signing ICF
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Non-metastatic operable Stage II−III breast cancer
• Histologically documented TNBC (negative HER2, ER, and PgR status)
• Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen
• Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing
mastectomy.
• Pathological tumor-node-metastasis staging (Union for International Cancer Control/American Joint Committee on Cancer
[UICC/AJCC], 8th edition): Patient must have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection for
evaluation of pathologic nodal status.
• Patients with synchronous bilateral invasive disease are eligible only if all bilateral invasive lesions are histologically confirmed
as triple negative by central lab and have completed adequate pathological tumor-node metastasis staging bilaterally as
described above.
• No more than 8 weeks (56 days) may elapse between definitive breast surgery (or the last surgery with curative intent if
additional resection is required for breast cancer) and randomization.
• Baseline LVEF ≥ 53% measured by ECHO (preferred) or MUGA scans Baseline LVEF to be conducted within 28 days prior to
initiation of study treatment.
• Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B
virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total
HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at
screening
• The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
• Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred)
or at least 25 unstained slides, with an associated pathology report documenting locally assessed ER, PgR, and HER2 negativity.
Patients with 20 to 25 unstained slides available at baseline may be eligible upon discussion with the Medical Monitor.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, or 6 months after the last dose of paclitaxel or doxorubicin, or 12 months after the last dose of cyclophosphamide, whichever is later.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
• Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or have not undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of PRO questionnaires.
• Signed Informed Consent Form (ICF)
• Ability to comply with protocol, in the investigator’s judgment
• Women or men aged ≥ 18 years at time of signing ICF
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Non-metastatic operable Stage II−III breast cancer
• Histologically documented TNBC (negative HER2, ER, and PgR status)
• Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen
• Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing
mastectomy.
• Pathological tumor-node-metastasis staging (Union for International Cancer Control/American Joint Committee on Cancer
[UICC/AJCC], 8th edition): Patient must have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection for
evaluation of pathologic nodal status.
• Patients with synchronous bilateral invasive disease are eligible only if all bilateral invasive lesions are histologically confirmed
as triple negative by central lab and have completed adequate pathological tumor-node metastasis staging bilaterally as
described above.
• No more than 8 weeks (56 days) may elapse between definitive breast surgery (or the last surgery with curative intent if
additional resection is required for breast cancer) and randomization.
• Baseline LVEF ≥ 53% measured by ECHO (preferred) or MUGA scans Baseline LVEF to be conducted within 28 days prior to
initiation of study treatment.
• Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B
virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total
HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at
screening
• The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
• Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred)
or at least 25 unstained slides, with an associated pathology report documenting locally assessed ER, PgR, and HER2 negativity.
Patients with 20 to 25 unstained slides available at baseline may be eligible upon discussion with the Medical Monitor.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, or 6 months after the last dose of paclitaxel or doxorubicin, or 12 months after the last dose of cyclophosphamide, whichever is later.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
• Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or have not undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of PRO questionnaires.
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
• Prior history of invasive breast cancer
• Any T4 clinical tumor as defined by tumor-node metastasis classification in UICC/AJCC,8th edition, including inflammatory breast cancer
• For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment
• Previous therapy with anthracyclines or taxanes for any malignancy
• History of DCIS and/or LCIS that was treated with any form of systemic, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developedPatients who had their DCIS/LCIS treated only with surgery and/or contralateral DCIS
treated with RT are allowed to enter the study.
• Contraindication to RT when adjuvant RT is clinically indicated
• Cardiopulmonary dysfunction as defined by any of the following prior to randomization:History of NCI CTCAE v4.0 Grade ≥ 3 symptomatic congestive heart failure or NewYork Heart Association (NYHA) criteria Class ≥ II Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at
rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 Mobitz 2, or third-degreeAV-block])Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac
arrhythmia, or cardiac ischemiaMyocardial infarction within 12 months prior to randomization Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) Evidence of transmural infarction on ECG
Requirement for oxygen therapy
• Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
• Known allergy or hypersensitivity to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the paclitaxel (e.g., polyoxyl 35 castor oil), cyclophosphamide, or doxorubicin/epirubicin formulations
• Known allergy or hypersensitivity to filgrastim or pegfilgrastim or GM-CSF formulations
• Active or history of autoimmune disease or immune deficiency, including, but not limited to,myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, or multiple sclerosis with the
following exceptions:Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone are eligible for this study.Patients with controlled Type I diabetes mellitus who are on an insulin regimen may be eligible for this study.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans),drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Current treatment with anti-viral therapy for HBV
• Urinary outflow obstruction
• Active tuberculosis
• Severe infections within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment
• Prior allogeneic stem cell or solid organ transplant
• Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or within 5 months after the last dose of atezolizumab
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment
complications
• Prior treatment with CD137 agonists or immune checkpoint−blockade therapies, including anti-CD40, anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferons,interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
• Treatment with systemic immunosuppressive medications (including, but not limited to,prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] alpha agents) within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Medical Monitor. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
• Pregnant or lactating, or intending to become pregnant during the study
•Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease
• Prior history of invasive breast cancer
• Any T4 clinical tumor as defined by tumor-node metastasis classification in UICC/AJCC,8th edition, including inflammatory breast cancer
• For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment
• Previous therapy with anthracyclines or taxanes for any malignancy
• History of DCIS and/or LCIS that was treated with any form of systemic, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developedPatients who had their DCIS/LCIS treated only with surgery and/or contralateral DCIS
treated with RT are allowed to enter the study.
• Contraindication to RT when adjuvant RT is clinically indicated
• Cardiopulmonary dysfunction as defined by any of the following prior to randomization:History of NCI CTCAE v4.0 Grade ≥ 3 symptomatic congestive heart failure or NewYork Heart Association (NYHA) criteria Class ≥ II Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at
rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 Mobitz 2, or third-degreeAV-block])Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac
arrhythmia, or cardiac ischemiaMyocardial infarction within 12 months prior to randomization Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) Evidence of transmural infarction on ECG
Requirement for oxygen therapy
• Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
• Known allergy or hypersensitivity to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the paclitaxel (e.g., polyoxyl 35 castor oil), cyclophosphamide, or doxorubicin/epirubicin formulations
• Known allergy or hypersensitivity to filgrastim or pegfilgrastim or GM-CSF formulations
• Active or history of autoimmune disease or immune deficiency, including, but not limited to,myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, or multiple sclerosis with the
following exceptions:Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone are eligible for this study.Patients with controlled Type I diabetes mellitus who are on an insulin regimen may be eligible for this study.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans),drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Current treatment with anti-viral therapy for HBV
• Urinary outflow obstruction
• Active tuberculosis
• Severe infections within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment
• Prior allogeneic stem cell or solid organ transplant
• Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or within 5 months after the last dose of atezolizumab
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment
complications
• Prior treatment with CD137 agonists or immune checkpoint−blockade therapies, including anti-CD40, anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferons,interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
• Treatment with systemic immunosuppressive medications (including, but not limited to,prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] alpha agents) within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Medical Monitor. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
• Pregnant or lactating, or intending to become pregnant during the study
•Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease
The Estimated Number of Participants
-
Taiwan
80 participants
-
Global
2300 participants
