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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 (APHINITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01358877
Recruitment Status : Active, not recruiting
First Posted : May 24, 2011
Results First Posted : January 5, 2018
Last Update Posted : January 5, 2018
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: 5-Fluorouracil
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Doxorubicin
Drug: Epirubicin
Drug: Paclitaxel
Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The analysis included data up to a clinical data cut-off date of 19 December 2016.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Chemotherapy Participants received 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 + Trastuzumab + Chemotherapy Participants received placebo matched 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]).

Participant Flow:   Overall Study
    Pertuzumab + Trastuzumab + Chemotherapy   Placebo + Trastuzumab + Chemotherapy
STARTED   2400   2404 
Did Not Receive Study Drug   22   13 
Received Study Drug (Safety Population)   2364 [1]   2405 [2] 
COMPLETED   0   0 
NOT COMPLETED   2400   2404 
Death                80                89 
Ongoing follow-up for post-recurrence                87                108 
Ongoing follow-up for IDFS event                2084                2073 
Ongoing follow-up for overall survival                7                5 
Other                142                129 
[1] 24 placebo participants received at least 1 dose of pertuzumab and were included in pertuzumab arm.
[2] 38 pertuzumab participants did not receive pertuzumab and were included in placebo arm.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population included all randomized participants regardless of treatment received.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Chemotherapy Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 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 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 area under the curve (AUC) 6 (up to 900 mg).
Placebo + Trastuzumab + Chemotherapy Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 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 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 mg).
Total Total of all reporting groups

Baseline Measures
   Pertuzumab + Trastuzumab + Chemotherapy   Placebo + Trastuzumab + Chemotherapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 2400   2404   4804 
Age 
[Units: Years]
Mean (Standard Deviation)
 51.7  (10.9)   51.4  (10.7)   51.5  (10.8) 
Sex: Female, Male [1] 
[Units: Participants]
Count of Participants
     
Female      2397  99.9%      2396  99.7%      4793  99.8% 
Male      3   0.1%      8   0.3%      11   0.2% 
[1] ITT population


  Outcome Measures

1.  Primary:   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   [ Time Frame: 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) ]

2.  Primary:   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   [ Time Frame: 3 years ]

3.  Secondary:   Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings   [ Time Frame: 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) ]

4.  Secondary:   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   [ Time Frame: 3 years ]

5.  Secondary:   Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings   [ Time Frame: 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) ]

6.  Secondary:   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   [ Time Frame: 3 years ]

7.  Secondary:   Percentage of Participants Who Died   [ Time Frame: 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) ]

8.  Secondary:   Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3   [ Time Frame: 3 years ]

9.  Secondary:   Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings   [ Time Frame: 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) ]

10.  Secondary:   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   [ Time Frame: 3 years ]

11.  Secondary:   Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings   [ Time Frame: Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]

12.  Secondary:   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   [ Time Frame: 3 years ]

13.  Secondary:   Percentage of Participants With Primary Cardiac Event   [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]

14.  Secondary:   Percentage of Participants With Secondary Cardiac Event   [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]

15.  Secondary:   Change From Baseline in LVEF to Worst Post-Baseline Value   [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]

16.  Secondary:   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   [ Time Frame: 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 ]

17.  Secondary:   Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

18.  Secondary:   Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

19.  Secondary:   Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

20.  Secondary:   Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

21.  Secondary:   Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

22.  Secondary:   Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

23.  Secondary:   Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

24.  Secondary:   Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

25.  Secondary:   Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

26.  Secondary:   Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain   [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]

27.  Secondary:   Trough Serum Concentration (Cmin) of Pertuzumab   [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]

28.  Secondary:   Cmin of Trastuzumab   [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]

29.  Secondary:   Peak Serum Concentration (Cmax) of Pertuzumab   [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]

30.  Secondary:   Cmax of Trastuzumab   [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01358877     History of Changes
Other Study ID Numbers: BO25126
TOC4939G ( Other Identifier: Genentech )
2010-022902-41 ( EudraCT Number )
BIG 4-11 ( Other Identifier: Breast International Group )
First Submitted: May 20, 2011
First Posted: May 24, 2011
Results First Submitted: December 4, 2017
Results First Posted: January 5, 2018
Last Update Posted: January 5, 2018