Clinical Trials List
Protocol NumberFM-14-B02
NCT Number(ClinicalTrials.gov Identfier)NCT02620280
2016-06-01 - 2025-05-31
Phase III
Terminated5
ICD-10C50
Malignant neoplasm of breast
Neo-Adjuvant study with the PDL1-directed antibody in Triple Negative Locally Advanced Breast Cancer undergoing treatment with nabpaclitaxel and carboplatin
-
Trial Applicant
-
Sponsor
National Taiwan University Hospital
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Taipei Veterans General Hospital
Taiwan National PI
曾令民
Co-Principal Investigator
- 金光亮 Division of General Surgery
- 林燕淑 Division of General Surgery
- Yi-Fang Tsai Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- 邱仁輝 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
4 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chih-Jung Chen Division of General Surgery
- HWEI-CHUNG WANG Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Fu Ouyang Division of General Surgery
- Fang-Ming Chen Division of General Surgery
- Chieh-Han Chuang Division of General Surgery
- 甘蓉瑜 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 郭文宏 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- 蔡立威 Division of General Surgery
- 羅喬 Division of General Surgery
- 楊雅雯 Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Triple Negative Locally Advanced Breast Cancer
Objectives
Primary objective:
Compare Event Free Survival (EFS) in the 2 study arms from the time of
randomization
Secondary objectives:
Compare the rate of pathological complete response (pCR) defined as
ypT0-ypTis ypN0 at surgery
Compare clinical overall response (cOR) at the end of neo-adjuvant
therapy.
Compare Distant EFS (DEFS) from the time of randomization
Compare overall survival from the time of randomization
Evaluate tolerability of the treatment regimens in the different study arms
Conduct molecular and clinical analyses to assess the presence of
prognostic and/or predictive markers of benefit and/or resistance to the
study regimens and to improve our understanding of breast cancer
disease.
Test Drug
atezolizumab (MPDL3280A)
Active Ingredient
anti PD-L1 antibody
Dosage Form
Injection
Dosage
60mg/mL
Endpoints
Primary Outcome Measures :
1. Event Free Survival (EFS) [ Time Frame: 5 years after the randomization of the last patient ]
To compare EFS (disease progression while on neoadjuvant therapy or disease recurrence after surgery) in the two study arms
Secondary Outcome Measures :
1. Pathological complete response (pCR) [ Time Frame: At surgery, an expected average of 34 weeks after the randomization of the last patient ]
Assess the rate of pCR defined as ypT0-ypTis ypN0 at surgery in the two treatment arms
2. Clinical objective response [ Time Frame: Participants will be followed for the duration of neoadjuvant therapy, an expected average of 26 weeks ]
Assess the clinical response rate after neoadjuvant therapy
3. Distant Event Free Survival (DEFS) [ Time Frame: 5 years after the randomization of the last patients ]
To compare the DEFS, defined as the occurrence of distant disease progression while on neoadjuvant therapy or distant recurrence after surgery in the two treatment arms
4. Number of participants with adverse events as a Measure of Safety and Tolerability [ Time Frame: Participants wil be followed for up to 5 years from the last randomized patient ]
Number of participants with Adverse Events and related grade
1. Event Free Survival (EFS) [ Time Frame: 5 years after the randomization of the last patient ]
To compare EFS (disease progression while on neoadjuvant therapy or disease recurrence after surgery) in the two study arms
Secondary Outcome Measures :
1. Pathological complete response (pCR) [ Time Frame: At surgery, an expected average of 34 weeks after the randomization of the last patient ]
Assess the rate of pCR defined as ypT0-ypTis ypN0 at surgery in the two treatment arms
2. Clinical objective response [ Time Frame: Participants will be followed for the duration of neoadjuvant therapy, an expected average of 26 weeks ]
Assess the clinical response rate after neoadjuvant therapy
3. Distant Event Free Survival (DEFS) [ Time Frame: 5 years after the randomization of the last patients ]
To compare the DEFS, defined as the occurrence of distant disease progression while on neoadjuvant therapy or distant recurrence after surgery in the two treatment arms
4. Number of participants with adverse events as a Measure of Safety and Tolerability [ Time Frame: Participants wil be followed for up to 5 years from the last randomized patient ]
Number of participants with Adverse Events and related grade
Inclution Criteria
Inclusion Criteria
Patients must meet ALL of the following criteria in order to be eligible for this
study:
1. Female patients aged 18 years or older with locally advanced or
inflammatory breast cancers (stage III A-C according to AJCC) suitable
for neoadjuvant treatment
2. Histologically confirmed unilateral breast cancer with invasive ductal
histology not otherwise specified (NOS) of high proliferation or grade
3. HER2 negative disease defined as 0-1+ by immunohistochemistry or
2+ by immunohistochemistry without HER2 amplification by either In
Situ Hybridization (ISH) or other amplification tests done locally.
4. Negative estrogen receptor (ER) and progesterone receptor (PgR),
both < 1% locally assessed
5. Representative paraffin-embedded (FFPE) tumor block taken at
diagnostic biopsy for confirmation of HER2, ER and PgR eligibility, for
assessment of PDL-1 expression and for further exploratory biomarker
evaluation is mandatory. Note: FFPE tumor blocks are also mandatory
after the first cycle of therapy; surgery tissue (residual tumor or tumor
bed in case of pCR) is also mandatory
6. ECOG performance status 0 or 1
7. Written informed consent to participate in the trial (approved by the
Institutional Review Board [IRB]/ Independent Ethics Committee [IEC])
obtained prior to any study specific screening procedures
8. Willing and able to comply with the protocol
9. Consent to the collection of blood samples mandatorily before starting
neoadjuvant treatment, after the first cycle of therapy, at the end of
neoadjuvant treatment (before surgery), at the end of adjuvant
chemotherapy and once a year for 2 years during follow-up
10. For women who are not postmenopausal (≥ 12 months of non-therapyinduced amenorrhea) or surgically sterile (absence of ovaries and/or
uterus): agreement to remain abstinent or use single or combined
contraceptive methods that result in a failure rate of < 1% per year
during the treatment period and for at least 90 days after the last dose
of study drug. Abstinence is only acceptable if it is in line with the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception. Examples of
contraceptive methods with a failure rate of < 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use
of combined oral or injected hormonal contraceptives, and certain
intrauterine devices. Alternatively, two methods (e.g., two barrier
methods such as a condom and a cervical cap) may be combined to
achieve a failure rate of < 1% per year. Barrier methods must always
be supplemented with the use of a spermicide
Patients must meet ALL of the following criteria in order to be eligible for this
study:
1. Female patients aged 18 years or older with locally advanced or
inflammatory breast cancers (stage III A-C according to AJCC) suitable
for neoadjuvant treatment
2. Histologically confirmed unilateral breast cancer with invasive ductal
histology not otherwise specified (NOS) of high proliferation or grade
3. HER2 negative disease defined as 0-1+ by immunohistochemistry or
2+ by immunohistochemistry without HER2 amplification by either In
Situ Hybridization (ISH) or other amplification tests done locally.
4. Negative estrogen receptor (ER) and progesterone receptor (PgR),
both < 1% locally assessed
5. Representative paraffin-embedded (FFPE) tumor block taken at
diagnostic biopsy for confirmation of HER2, ER and PgR eligibility, for
assessment of PDL-1 expression and for further exploratory biomarker
evaluation is mandatory. Note: FFPE tumor blocks are also mandatory
after the first cycle of therapy; surgery tissue (residual tumor or tumor
bed in case of pCR) is also mandatory
6. ECOG performance status 0 or 1
7. Written informed consent to participate in the trial (approved by the
Institutional Review Board [IRB]/ Independent Ethics Committee [IEC])
obtained prior to any study specific screening procedures
8. Willing and able to comply with the protocol
9. Consent to the collection of blood samples mandatorily before starting
neoadjuvant treatment, after the first cycle of therapy, at the end of
neoadjuvant treatment (before surgery), at the end of adjuvant
chemotherapy and once a year for 2 years during follow-up
10. For women who are not postmenopausal (≥ 12 months of non-therapyinduced amenorrhea) or surgically sterile (absence of ovaries and/or
uterus): agreement to remain abstinent or use single or combined
contraceptive methods that result in a failure rate of < 1% per year
during the treatment period and for at least 90 days after the last dose
of study drug. Abstinence is only acceptable if it is in line with the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception. Examples of
contraceptive methods with a failure rate of < 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use
of combined oral or injected hormonal contraceptives, and certain
intrauterine devices. Alternatively, two methods (e.g., two barrier
methods such as a condom and a cervical cap) may be combined to
achieve a failure rate of < 1% per year. Barrier methods must always
be supplemented with the use of a spermicide
Exclusion Criteria
Exclusion Criteria
Patients meeting any ONE of the following criteria are not eligible for this study:
1. Evidence of bilateral breast cancer or metastatic disease (M1)
2. Cases with an histology different from invasive ductal NOS of high
proliferation or grade
3. Patients with HER2-positive disease according to ASCO/CAP
guidelines 2013 (defined as IHC 3+ or ISH positive according to the
Guidelines) are considered not eligible for the study
4. Pregnant or lactating women. Documentation of a negative pregnancy
test must be available for premenopausal women with intact
reproductive organs and for women less than one year after the last
menstrual cycle
5. Previous treatment with chemotherapy, hormonal therapy or an
investigational drug for any type of malignancy
6. Previous investigational treatment for any condition within 4 weeks of
randomization date
7. Administration of a live, attenuated vaccine within 4 weeks before cycle
1 Day 1 or anticipation that such a live attenuated vaccine will be
required during the study
8. Previous or concomitant invasive malignancy of any other type or
previous invasive breast cancer. Patients with curatively treated basal
cell carcinoma of the skin or in situ cervix cancer are generally eligible
9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason
10. History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
11. Known hypersensitivity or allergy to biopharmaceuticals produced in
Chinese hamster ovary cells or any component of the MPDL3280A
formulation
12. Patients with prior allogeneic stem cell or solid organ transplantation
13. History of autoimmune disease including, but not limited to, systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome,
Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, GuillainBarré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
14. History of idiopathic pulmonary fibrosis (including bronchiolitis
obliterans with organizing pneumonia) or evidence of active
pneumonitis on screening chest computed tomography scan
15. Known clinically significant liver disease, including active viral,
alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver
disease
16. History of HIV infection, active hepatitis B (chronic or acute), or hepatitis
C infection. Patients with past or resolved hepatitis B infection (defined
as having a negative HBsAg test and a positive hepatitis B core antigen
[anti-HBc] test) are eligible.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction assay (PCR) is negative for HCV RNA
17. Active tuberculosis
18. Severe infections within 4 weeks prior to cycle 1 Day 1, including, but
not limited to, hospitalization for complications of infection, bacteremia,
or severe pneumonia. Signs or symptoms of significant infection within
2 weeks prior to cycle 1 Day 1
19. Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
20. Other serious illness or medical condition including: history of
documented congestive cardiac failure; New York Heart Association
(NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal
medication or unstable angina within 6 months prior to cycle 1 Day 1;
evidence of transmural infarction on ECG; myocardial infarction stroke
or transient ischemic attack (TIA) within 6 months prior to cycle 1 Day
1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic
>100 mm Hg; however, patients with hypertension which is well
controlled on medication are eligible); clinically significant valvular heart
disease; high-risk uncontrolled arrhythmias
21. Patients with a history of uncontrolled seizures, central nervous system
disorders or psychiatric disability judged by the investigator to be
clinically significant and precluding informed consent or adversely
affecting compliance with study drugs
22. Serious uncontrolled infections (bacterial or viral) or poorly controlled
diabetes mellitus
23. Any of the following abnormal baseline hematological values:
a. White blood count (WBC) < 2.5 x 109/L
b. Absolute Neutrophil Count (ANC) < 1.5 109/L
c. Lymphocyte count < 0.5 x 109/L
d. Platelet count < 100 109/L
e. Hemoglobin (Hb) < 10 g/dL
24. Any of the following abnormal baseline laboratory tests
a. Serum total bilirubin > 1.5 ULN (upper limit of normal) (except
for patients with clearly documented Gilbert’s syndrome)
b. Alanine transaminase (ALT) or aspartate transaminase (AST) >
1.25 ULN
c. Alkaline phosphatase > 2.5 ULN
d. Serum creatinine > 1.5 ULN
e. INR and aPTT > 1.5 × ULN within 2 weeks prior to enrollment.
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation
should be on a stable dose.
25. Baseline left ventricular ejection fraction (LVEF) < 50% by
echocardiography or multi-gated scintigraphic scan (MUGA)
26. Major surgical procedure within 28 days prior to cycle 1 Day 1 or
anticipation of need for a major surgical procedure during the course of
the study
27. Influenza vaccination should be given during influenza season only
(approximately October to March). Patients must not receive live,
attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to
cycle 1 Day 1 or at any time during the study.
Patients meeting any ONE of the following criteria are not eligible for this study:
1. Evidence of bilateral breast cancer or metastatic disease (M1)
2. Cases with an histology different from invasive ductal NOS of high
proliferation or grade
3. Patients with HER2-positive disease according to ASCO/CAP
guidelines 2013 (defined as IHC 3+ or ISH positive according to the
Guidelines) are considered not eligible for the study
4. Pregnant or lactating women. Documentation of a negative pregnancy
test must be available for premenopausal women with intact
reproductive organs and for women less than one year after the last
menstrual cycle
5. Previous treatment with chemotherapy, hormonal therapy or an
investigational drug for any type of malignancy
6. Previous investigational treatment for any condition within 4 weeks of
randomization date
7. Administration of a live, attenuated vaccine within 4 weeks before cycle
1 Day 1 or anticipation that such a live attenuated vaccine will be
required during the study
8. Previous or concomitant invasive malignancy of any other type or
previous invasive breast cancer. Patients with curatively treated basal
cell carcinoma of the skin or in situ cervix cancer are generally eligible
9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason
10. History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
11. Known hypersensitivity or allergy to biopharmaceuticals produced in
Chinese hamster ovary cells or any component of the MPDL3280A
formulation
12. Patients with prior allogeneic stem cell or solid organ transplantation
13. History of autoimmune disease including, but not limited to, systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome,
Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, GuillainBarré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
14. History of idiopathic pulmonary fibrosis (including bronchiolitis
obliterans with organizing pneumonia) or evidence of active
pneumonitis on screening chest computed tomography scan
15. Known clinically significant liver disease, including active viral,
alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver
disease
16. History of HIV infection, active hepatitis B (chronic or acute), or hepatitis
C infection. Patients with past or resolved hepatitis B infection (defined
as having a negative HBsAg test and a positive hepatitis B core antigen
[anti-HBc] test) are eligible.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction assay (PCR) is negative for HCV RNA
17. Active tuberculosis
18. Severe infections within 4 weeks prior to cycle 1 Day 1, including, but
not limited to, hospitalization for complications of infection, bacteremia,
or severe pneumonia. Signs or symptoms of significant infection within
2 weeks prior to cycle 1 Day 1
19. Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
20. Other serious illness or medical condition including: history of
documented congestive cardiac failure; New York Heart Association
(NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal
medication or unstable angina within 6 months prior to cycle 1 Day 1;
evidence of transmural infarction on ECG; myocardial infarction stroke
or transient ischemic attack (TIA) within 6 months prior to cycle 1 Day
1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic
>100 mm Hg; however, patients with hypertension which is well
controlled on medication are eligible); clinically significant valvular heart
disease; high-risk uncontrolled arrhythmias
21. Patients with a history of uncontrolled seizures, central nervous system
disorders or psychiatric disability judged by the investigator to be
clinically significant and precluding informed consent or adversely
affecting compliance with study drugs
22. Serious uncontrolled infections (bacterial or viral) or poorly controlled
diabetes mellitus
23. Any of the following abnormal baseline hematological values:
a. White blood count (WBC) < 2.5 x 109/L
b. Absolute Neutrophil Count (ANC) < 1.5 109/L
c. Lymphocyte count < 0.5 x 109/L
d. Platelet count < 100 109/L
e. Hemoglobin (Hb) < 10 g/dL
24. Any of the following abnormal baseline laboratory tests
a. Serum total bilirubin > 1.5 ULN (upper limit of normal) (except
for patients with clearly documented Gilbert’s syndrome)
b. Alanine transaminase (ALT) or aspartate transaminase (AST) >
1.25 ULN
c. Alkaline phosphatase > 2.5 ULN
d. Serum creatinine > 1.5 ULN
e. INR and aPTT > 1.5 × ULN within 2 weeks prior to enrollment.
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation
should be on a stable dose.
25. Baseline left ventricular ejection fraction (LVEF) < 50% by
echocardiography or multi-gated scintigraphic scan (MUGA)
26. Major surgical procedure within 28 days prior to cycle 1 Day 1 or
anticipation of need for a major surgical procedure during the course of
the study
27. Influenza vaccination should be given during influenza season only
(approximately October to March). Patients must not receive live,
attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to
cycle 1 Day 1 or at any time during the study.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
272 participants
