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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01358877




Registration number
NCT01358877
Ethics application status
Date submitted
20/05/2011
Date registered
24/05/2011
Date last updated
9/06/2020

Titles & IDs
Public title
A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer
Scientific title
A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
Secondary ID [1] 0 0
TOC4939G
Secondary ID [2] 0 0
BO25126
Universal Trial Number (UTN)
Trial acronym
APHINITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluorouracil
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Docetaxel
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Epirubicin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Placebo
Treatment: Drugs - Trastuzumab

Experimental: Pertuzumab + Trastuzumab + Chemotherapy - Participants will receive pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).

Placebo Comparator: Placebo + Trastuzumab + Chemotherapy - Participants will receive placebo matching to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]).


Treatment: Drugs: 5-Fluorouracil
5-Fluorouracil will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Carboplatin
Carboplatin will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Docetaxel
Docetaxel will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Epirubicin
Epirubicin will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Placebo
Placebo will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.
Timepoint [1] 0 0
Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Primary outcome [2] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event was defined as 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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event.
Timepoint [2] 0 0
3 years
Secondary outcome [1] 0 0
Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as 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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Timepoint [1] 0 0
Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary outcome [2] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC was defined as 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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Percentage of participants with DFS event is reported. DFS event was defined as 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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
Timepoint [3] 0 0
Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary outcome [4] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS was defined as 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); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Percentage of Participants Who Died - Percentage of participants who died due to any cause is reported.
Timepoint [5] 0 0
Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary outcome [6] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3 - The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years.
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
Timepoint [7] 0 0
Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary outcome [8] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence.
Timepoint [9] 0 0
Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary outcome [10] 0 0
Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings - Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence.
Timepoint [10] 0 0
3 years
Secondary outcome [11] 0 0
Percentage of Participants With Primary Cardiac Event - Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.
Timepoint [11] 0 0
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary outcome [12] 0 0
Percentage of Participants With Secondary Cardiac Event - Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB).
Timepoint [12] 0 0
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary outcome [13] 0 0
Change From Baseline in LVEF to Worst Post-Baseline Value - LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
Timepoint [13] 0 0
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary outcome [14] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score - EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement.
Timepoint [14] 0 0
Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36
Secondary outcome [15] 0 0
Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores - EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning and positive values indicated improvement.
Timepoint [15] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [16] 0 0
Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores - EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 disease/treatment-related symptom scores were linearly transformed on a scale of 0 to 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicated improvement in symptoms and positive values indicated worsening of symptoms.
Timepoint [16] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [17] 0 0
Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores - EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties and positive values indicated worsening of financial difficulties.
Timepoint [17] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [18] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score - EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
Timepoint [18] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [19] 0 0
Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score - EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
Timepoint [19] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [20] 0 0
Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain - EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding.
Timepoint [20] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [21] 0 0
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain - EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding.
Timepoint [21] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [22] 0 0
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain - EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding.
Timepoint [22] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [23] 0 0
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain - EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding.
Timepoint [23] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [24] 0 0
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain - EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding.
Timepoint [24] 0 0
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary outcome [25] 0 0
Trough Serum Concentration (Cmin) of Pertuzumab
Timepoint [25] 0 0
Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary outcome [26] 0 0
Cmin of Trastuzumab
Timepoint [26] 0 0
Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary outcome [27] 0 0
Peak Serum Concentration (Cmax) of Pertuzumab
Timepoint [27] 0 0
Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary outcome [28] 0 0
Cmax of Trastuzumab
Timepoint [28] 0 0
Cycles 1, 10 and 15 (Cycle length=21 days)

Eligibility
Key inclusion criteria
- Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is
histologically confirmed, and adequately excised

- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
(</=) 1

- Known hormone receptor status (estrogen receptor and progesterone receptor)

- The interval between definitive surgery for breast cancer and the first dose of
chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy
must be administered within 7 days of randomization or on Day 56, whichever occurs
first

- Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55
percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA)
Scan

- Confirmed HER2 positive status

- Completion of all necessary baseline laboratory and radiologic investigations prior to
randomization

- Women of childbearing potential and male participants with partners of childbearing
potential must agree to use effective contraception (as defined by the protocol) by
the participant and/or partner for the duration of the study treatment and for at
least 7 months after the last dose of study drug
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of any prior (ipsi- and/or contralateral) invasive breast cancer

- History of non-breast malignancies within the 5 years prior to study entry, except for
carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and
basal cell and squamous cell carcinomas of the skin

- Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant
metastasis (TNM), including inflammatory breast cancer

- Any node-negative tumor

- Any previous systemic chemotherapy for cancer or radiotherapy for cancer

- Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy
for cancer

- Concurrent anti-cancer treatment in another investigational trial

- Serious cardiac or cardiovascular disease or condition

- Other concurrent serious diseases that may interfere with planned treatment including
severe pulmonary conditions/illness

- Abnormal laboratory tests immediately prior to randomization

- Pregnant or lactating women

- Sensitivity to any of the study medications or any of the ingredients or excipients of
these medications

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Lismore Base Hospital; Cancer Care & Haematology Unit - Lismore
Recruitment hospital [2] 0 0
Mater Misericordiae Hospital; Chemotherapy Cottage - Sydney
Recruitment hospital [3] 0 0
Newcastle Mater Misericordiae Hospital; Oncology - Waratah
Recruitment hospital [4] 0 0
Westmead Hospital; Medical Oncology and Pallative Care - Westmead
Recruitment hospital [5] 0 0
Wesley Medical Centre; Clinic For Haematology and Oncology - Auchenflower
Recruitment hospital [6] 0 0
Mater Hospital; Oncology - Brisbane
Recruitment hospital [7] 0 0
Royal Adelaide Hospital; Oncology - Adelaide
Recruitment hospital [8] 0 0
Royal Hobart Hospital; Medical Oncology - Hobart
Recruitment hospital [9] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment hospital [10] 0 0
Geelong Hospital; Andrew Love Cancer Centre - Geelong
Recruitment hospital [11] 0 0
Austin Hospital; Medical Oncology - Heidelberg
Recruitment hospital [12] 0 0
Peter Maccallum Cancer Institute; Medical Oncology - Melbourne
Recruitment hospital [13] 0 0
Sir Charles Gairdner Hospital; Medical Oncology - Perth
Recruitment postcode(s) [1] 0 0
2480 - Lismore
Recruitment postcode(s) [2] 0 0
2060 - Sydney
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4066 - Auchenflower
Recruitment postcode(s) [6] 0 0
4101 - Brisbane
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3220 - Geelong
Recruitment postcode(s) [11] 0 0
3084 - Heidelberg
Recruitment postcode(s) [12] 0 0
3000 - Melbourne
Recruitment postcode(s) [13] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Hungary
State/province [200] 0 0
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Hungary
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Hungary
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Hungary
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Israel
State/province [210] 0 0
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Country [211] 0 0
Israel
State/province [211] 0 0
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State/province [212] 0 0
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State/province [213] 0 0
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Japan
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Country [237] 0 0
Japan
State/province [237] 0 0
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Country [238] 0 0
Japan
State/province [238] 0 0
Niigata
Country [239] 0 0
Japan
State/province [239] 0 0
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Country [240] 0 0
Japan
State/province [240] 0 0
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Country [241] 0 0
Japan
State/province [241] 0 0
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Country [242] 0 0
Japan
State/province [242] 0 0
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Country [243] 0 0
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State/province [243] 0 0
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Mexico
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Mexico
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Mexico
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Country [250] 0 0
Mexico
State/province [250] 0 0
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Country [251] 0 0
Mexico
State/province [251] 0 0
León
Country [252] 0 0
Mexico
State/province [252] 0 0
Mexico DF
Country [253] 0 0
Mexico
State/province [253] 0 0
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Country [254] 0 0
Mexico
State/province [254] 0 0
Oaxaca
Country [255] 0 0
Mexico
State/province [255] 0 0
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Country [256] 0 0
Mexico
State/province [256] 0 0
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Country [257] 0 0
Netherlands
State/province [257] 0 0
Alkmaar
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Netherlands
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Breda
Country [259] 0 0
Netherlands
State/province [259] 0 0
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Netherlands
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Maastricht
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Zwolle
Country [262] 0 0
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New Zealand
State/province [263] 0 0
Palmerston North
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Panama
State/province [264] 0 0
Panama
Country [265] 0 0
Peru
State/province [265] 0 0
Lima
Country [266] 0 0
Peru
State/province [266] 0 0
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Trujillo
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Philippines
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Poland
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Romania
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Romania
State/province [278] 0 0
Cluj Napoca
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Romania
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Cluj-Napoca
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Romania
State/province [280] 0 0
Iasi
Country [281] 0 0
Russian Federation
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Kazan
Country [282] 0 0
Russian Federation
State/province [282] 0 0
Moscow
Country [283] 0 0
Russian Federation
State/province [283] 0 0
Pyatigorsk
Country [284] 0 0
Russian Federation
State/province [284] 0 0
Samara
Country [285] 0 0
Russian Federation
State/province [285] 0 0
Stavropol
Country [286] 0 0
Russian Federation
State/province [286] 0 0
Tula
Country [287] 0 0
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State/province [287] 0 0
Ljubljana
Country [288] 0 0
South Africa
State/province [288] 0 0
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Country [289] 0 0
South Africa
State/province [289] 0 0
Parktown, Johannesburg
Country [290] 0 0
South Africa
State/province [290] 0 0
Pretoria
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Breast International Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and
efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in
participants with operable HER2-positive primary breast cancer. This study will be carried
out in collaboration with the Breast International Group (BIG).
Trial website
https://clinicaltrials.gov/show/NCT01358877
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications