Clinical Trials List
Protocol NumberWO40324
NCT Number(ClinicalTrials.gov Identfier)NCT03493854
Completed
2018-07-01 - 2023-06-02
Phase III
Terminated3
ICD-10C50
Malignant neoplasm of breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A PHASE III, RANDOMIZED, MULTICENTER, OPEN-LABEL, TWO-ARM STUDY TO EVALUATE THE PHARMACOKINETICS, EFFICACY, AND SAFETY OF SUBCUTANEOUS ADMINISTRATION OF THE FIXED-DOSE COMBINATION OF PERTUZUMAB AND TRASTUZUMAB IN COMBINATION WITH CHEMOTHERAPY IN PATIENTS WITH HER2-POSITIVE EARLY BREAST CANCER
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Trial Applicant
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 金光亮 Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- Yi-Fang Tsai Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- 邱仁輝 Division of General Surgery
- 賴亦貞 Division of General Surgery
- 林燕淑 Division of General Surgery
The Actual Total Number of Participants Enrolled
8 Completed
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chen-Teng Wu Division of General Surgery
- Liang-Chih Liu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Yao-Chung Wu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Completed
Principal Investigator
Shin-Cheh Chen
Linkou Chang Gung Medical Foundation
Taiwan National PI
陳訓徹
Co-Principal Investigator
- 沈士哲 Division of General Surgery
- Yung-Chang Lin Division of Hematology & Oncology
- 周旭桓 Division of General Surgery
- Chi-Chang Yu Division of General Surgery
- Wen-Chi Shen Division of Hematology & Oncology
- Wen-Ling Kuo Division of General Surgery
- 翁世樺 Division of Others
The Actual Total Number of Participants Enrolled
4 Completed
Audit
None
Condition/Disease
HER2-POSITIVE EARLY BREAST CANCER
Objectives
This study will evaluate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for SC administration compared with the Perjeta IV and Herceptin IV formulations in patients with HER2-positive early breat cancer (EBC).
Test Drug
Pertuzumab and Trastuzumab FDC, Perjeta, Herceptin, Cyclophosphamide, Paclitaxel, Docetaxel, Doxorubincin
Active Ingredient
Dosage Form
Dosage
Pertuzumab 1200 mg and trastuzumab 600 mg/15 ml
Pertuzumab 600 mg and trastuzumab 600 mg/10 ml
420 mg/14 ml
150
600 mg/5 ml
1000
80 mg/4 ml
50 mg/25 ml
150 mg/25 ml
Pertuzumab 600 mg and trastuzumab 600 mg/10 ml
420 mg/14 ml
150
600 mg/5 ml
1000
80 mg/4 ml
50 mg/25 ml
150 mg/25 ml
Endpoints
To demonstrate the non-inferiority of the Cycle 7 (pre-dose Cycle 8) serum pertuzumab Ctrough of pertuzumab SC within the FDC compared with Perjeta IV
To demonstrate the non-inferiority of the Cycle 7 (pre-dose Cycle 8) serum trastuzumab Ctrough of trastuzumab SC within the FDC compared with Herceptin IV
To evaluate the efficacy of the SC FDC of pertuzumab and trastuzumab chemotherapy compared with Perjeta IV and Herceptin IV chemotherapy
To evaluate the safety of the SC FDC of pertuzumab and trastuzumab compared with Perjeta IV and Herceptin IV
To demonstrate the non-inferiority of the Cycle 7 (pre-dose Cycle 8) serum trastuzumab Ctrough of trastuzumab SC within the FDC compared with Herceptin IV
To evaluate the efficacy of the SC FDC of pertuzumab and trastuzumab chemotherapy compared with Perjeta IV and Herceptin IV chemotherapy
To evaluate the safety of the SC FDC of pertuzumab and trastuzumab compared with Perjeta IV and Herceptin IV
Inclution Criteria
Patients must meet the following criteria for study entry:
Signed Informed Consent Form
Age 18 years at time of signing Informed Consent Form
Ability to comply with the study protocol, in the investigator’s judgment
Female and male patients with Stage IIIIIC (T2T4, N0N3, M0), locally advanced,
inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast
cancer
Patients with inflammatory breast cancer must be able to have a core-needle
biopsy
Primary tumor 2 cm in diameter, or node-positive (clinically, on imaging, and on
cytology/histopathology)
HER2-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by IHC and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
Patients with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided at least one focus is sampled and centrally confirmed as HER2 positive.
Hormone receptor status of the primary tumor, centrally confirmed
Hormone receptor-positive status can be determined by either known
ER-positive and/or known PgR-positive status. Hormone receptor-negative
status must be determined by both known ER-negative and known
PgR-negative status
Patient agreement to undergo mastectomy or breast conserving surgery after
neoadjuvant therapy
Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research (e.g., PIK3A mutational analyses)
Baseline LVEF 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of 1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy
A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of highly effective non-hormonal contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and 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 (see Section 5.1.3).
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and 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 (see section 5.1.3).
A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women 12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
No major surgical procedure unrelated to breast cancer within 28 days prior to
randomization or anticipation of the need for major surgery during the course of study treatment
Signed Informed Consent Form
Age 18 years at time of signing Informed Consent Form
Ability to comply with the study protocol, in the investigator’s judgment
Female and male patients with Stage IIIIIC (T2T4, N0N3, M0), locally advanced,
inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast
cancer
Patients with inflammatory breast cancer must be able to have a core-needle
biopsy
Primary tumor 2 cm in diameter, or node-positive (clinically, on imaging, and on
cytology/histopathology)
HER2-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by IHC and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
Patients with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided at least one focus is sampled and centrally confirmed as HER2 positive.
Hormone receptor status of the primary tumor, centrally confirmed
Hormone receptor-positive status can be determined by either known
ER-positive and/or known PgR-positive status. Hormone receptor-negative
status must be determined by both known ER-negative and known
PgR-negative status
Patient agreement to undergo mastectomy or breast conserving surgery after
neoadjuvant therapy
Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research (e.g., PIK3A mutational analyses)
Baseline LVEF 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of 1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy
A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of highly effective non-hormonal contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and 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 (see Section 5.1.3).
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and 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 (see section 5.1.3).
A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women 12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
No major surgical procedure unrelated to breast cancer within 28 days prior to
randomization or anticipation of the need for major surgery during the course of study treatment
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
Stage IV (metastatic) breast cancer
Patients with a history of invasive breast cancer
Patients with a history of concurrent or previously treated non-breast malignancies
except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ
carcinomas, including cervix, colon, and skin
A patient with previous invasive non-breast cancer is eligible provided he/she
has been disease free for more than 5 years.
Patients who have received any previous systemic therapy (including chemotherapy,
immunotherapy, HER2-targeted agents, endocrine therapy (selective estrogen
receptor modulators, aromatase inhibitors, and antitumor vaccines) for treatment or
prevention of breast cancer, or radiation therapy for treatment of cancer
Patients who have a past history of ductal carcinoma in situ (DCIS) or lobular
carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
Patients are allowed to enter the study if treated with surgery alone.
Patients with high-risk for breast cancer who have received chemopreventative drugs in the past are not allowed to enter the study
Patients with multicentric (multiple tumors involving more than one quadrant) breast
cancer, unless all tumors are HER2-positive
Patients with bilateral breast cancer
Patients who have undergone an excisional biopsy of primary tumor and/or axillary
lymph nodes
Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
Patients with clinically negative axilla (by physical examination and
radiographic imaging) may undergo a core or needle biopsy procedure prior to
neoadjuvant systemic therapy if in keeping with local practice
Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
Treatment with any investigational drug within 28 days prior to randomization
Serious cardiac illness or medical conditions including, but not confined to, the
following:
– History of NCI CTCAE (v4) Grade 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class II
– 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, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block)
– Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality
– Angina pectoris requiring anti-anginal medication
– Clinically significant valvular heart disease
– Evidence of transmural infarction on ECG
– Evidence of myocardial infarction within 12 months prior to randomization
– Poorly controlled hypertension (e.g., systolic 180 mm Hg or diastolic 100 mmHg)
Inadequate bone marrow function, defined as:
– Absolute neutrophil count 1.5 109/L
– Platelet count 100109/L
– Hemoglobin 9 g/dL
Impaired liver function, defined as:
– Serum (total) bilirubin 1.25 upper limit of normal (ULN)
In case of Gilbert’s syndrome: a total bilirubin of 2 ULN is permitted.
– Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
1.25 ULN
– Albumin 25 g/L
Inadequate renal function with serum creatinine 1.5 ULN
Current severe, uncontrolled systemic disease that may interfere with planned
treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease;
wound-healing disorders)
Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy
Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug.
Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator’s judgment, precludes the patient’s safe participation in and completion of the study
Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
Concurrent, serious, uncontrolled infections, or known infection with HIV
Known hypersensitivity to study drugs, excipients, and/or murine proteins
Current chronic daily treatment with corticosteroids (dose 10 mg methylprednisolone or equivalent excluding inhaled steroids)
History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such
as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy),
coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic
testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or
long QT syndrome
Stage IV (metastatic) breast cancer
Patients with a history of invasive breast cancer
Patients with a history of concurrent or previously treated non-breast malignancies
except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ
carcinomas, including cervix, colon, and skin
A patient with previous invasive non-breast cancer is eligible provided he/she
has been disease free for more than 5 years.
Patients who have received any previous systemic therapy (including chemotherapy,
immunotherapy, HER2-targeted agents, endocrine therapy (selective estrogen
receptor modulators, aromatase inhibitors, and antitumor vaccines) for treatment or
prevention of breast cancer, or radiation therapy for treatment of cancer
Patients who have a past history of ductal carcinoma in situ (DCIS) or lobular
carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
Patients are allowed to enter the study if treated with surgery alone.
Patients with high-risk for breast cancer who have received chemopreventative drugs in the past are not allowed to enter the study
Patients with multicentric (multiple tumors involving more than one quadrant) breast
cancer, unless all tumors are HER2-positive
Patients with bilateral breast cancer
Patients who have undergone an excisional biopsy of primary tumor and/or axillary
lymph nodes
Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
Patients with clinically negative axilla (by physical examination and
radiographic imaging) may undergo a core or needle biopsy procedure prior to
neoadjuvant systemic therapy if in keeping with local practice
Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
Treatment with any investigational drug within 28 days prior to randomization
Serious cardiac illness or medical conditions including, but not confined to, the
following:
– History of NCI CTCAE (v4) Grade 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class II
– 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, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block)
– Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality
– Angina pectoris requiring anti-anginal medication
– Clinically significant valvular heart disease
– Evidence of transmural infarction on ECG
– Evidence of myocardial infarction within 12 months prior to randomization
– Poorly controlled hypertension (e.g., systolic 180 mm Hg or diastolic 100 mmHg)
Inadequate bone marrow function, defined as:
– Absolute neutrophil count 1.5 109/L
– Platelet count 100109/L
– Hemoglobin 9 g/dL
Impaired liver function, defined as:
– Serum (total) bilirubin 1.25 upper limit of normal (ULN)
In case of Gilbert’s syndrome: a total bilirubin of 2 ULN is permitted.
– Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
1.25 ULN
– Albumin 25 g/L
Inadequate renal function with serum creatinine 1.5 ULN
Current severe, uncontrolled systemic disease that may interfere with planned
treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease;
wound-healing disorders)
Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy
Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug.
Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator’s judgment, precludes the patient’s safe participation in and completion of the study
Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
Concurrent, serious, uncontrolled infections, or known infection with HIV
Known hypersensitivity to study drugs, excipients, and/or murine proteins
Current chronic daily treatment with corticosteroids (dose 10 mg methylprednisolone or equivalent excluding inhaled steroids)
History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such
as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy),
coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic
testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or
long QT syndrome
The Estimated Number of Participants
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Taiwan
18 participants
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Global
500 participants
