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A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

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ClinicalTrials.gov Identifier: NCT00950300
Recruitment Status : Completed
First Posted : July 31, 2009
Results First Posted : January 23, 2017
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: 5-Fluorouracil
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Epirubicin
Drug: Herceptin IV [trastuzumab]
Drug: Herceptin SC [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
A total of 833 participants were screened, out of which, 596 participants were enrolled into the study.

Reporting Groups
  Description
Herceptin IV + Chemotherapy Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 milligrams per meter-squared (mg/m^2) every 21 days for four cycles followed by 5-fluorouracil 500 mg/m^2, epirubicin 75 mg/m^2, and cyclophosphamide 500 mg/m^2 (FEC) every 21 days for four cycles. Herceptin was administered as 8 milligrams per kilogram (mg/kg) on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the Treatment-Free Follow-Up (TFFU) Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the Survival Follow-Up (SFU) Period.
Herceptin SC + Chemotherapy Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-milligram (mg) fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.

Participant Flow for 3 periods

Period 1:   Neoadjuvant/Adjuvant Treatment Periods
    Herceptin IV + Chemotherapy   Herceptin SC + Chemotherapy
STARTED   299   297 
Received Neoadjuvant Treatment   298   297 
Underwent Surgery   277   273 
Entered Adjuvant Treatment   277   274 
COMPLETED   257   255 
NOT COMPLETED   42   42 
Adverse Event or Intercurrent Illness                6                15 
Death                1                3 
Insufficient Therapeutic Response                3                0 
Violation of Selection Criteria                2                1 
Protocol Violation                1                0 
Participant Refusal/Withdrawal                4                5 
Lost to Follow-up                2                1 
Progression of Disease                12                11 
Recurrence of Disease                10                5 
Not Specified                1                1 

Period 2:   TFFU Period
    Herceptin IV + Chemotherapy   Herceptin SC + Chemotherapy
STARTED   265 [1]   268 [1] 
COMPLETED   165 [2]   161 [2] 
NOT COMPLETED   100   107 
Adverse Event or Intercurrent Illness                3                4 
Death                4                1 
Refused Treatment                10                11 
Failure to Return                16                16 
Recurrence of Disease                63                72 
Not Specified                4                3 
[1] Participants could withdraw from the study entirely or advance directly to the TFFU or SFU Period.
[2] Includes participants who completed either 2 years of follow-up or 5 years of follow-up.

Period 3:   SFU Period
    Herceptin IV + Chemotherapy   Herceptin SC + Chemotherapy
STARTED   118 [1]   123 [1] 
COMPLETED   40 [2]   45 [2] 
NOT COMPLETED   78   78 
Death                44                42 
Lost to Follow-up                30                28 
Withdrawal by Subject                4                8 
[1] Participants could withdraw from the study entirely or advance directly to the SFU Period.
[2] Includes participants who completed either 2 years of follow-up or 5 years of follow-up.



  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: All participants with at least one efficacy assessment after administration of the first treatment cycle.

Reporting Groups
  Description
Herceptin IV + Chemotherapy Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Herceptin SC + Chemotherapy Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Total Total of all reporting groups

Baseline Measures
   Herceptin IV + Chemotherapy   Herceptin SC + Chemotherapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 297   294   591 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.5  (10.83)   50.3  (11.08)   49.9  (10.95) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      297 100.0%      294 100.0%      591 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures

1.  Primary:   Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

2.  Primary:   Percentage of Participants With Pathological Complete Response (pCR)   [ Time Frame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline) ]

3.  Secondary:   Observed Ctrough of Trastuzumab After Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

4.  Secondary:   Predicted Ctrough of Trastuzumab Prior to Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

5.  Secondary:   Predicted Ctrough of Trastuzumab After Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

6.  Secondary:   Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

7.  Secondary:   Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery   [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

8.  Secondary:   Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

9.  Secondary:   Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

10.  Secondary:   Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]

11.  Secondary:   Cmax of Trastuzumab After Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

12.  Secondary:   Tmax of Trastuzumab After Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

13.  Secondary:   AUC21d of Trastuzumab After Surgery   [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]

14.  Secondary:   Percentage of Participants With Total Pathological Complete Response (tpCR)   [ Time Frame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline) ]

15.  Secondary:   Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline   [ Time Frame: Tumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall) ]

16.  Secondary:   Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline   [ Time Frame: Tumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall) ]

17.  Secondary:   Percentage of Participants Who Experienced a Protocol-Defined Event   [ Time Frame: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]

18.  Secondary:   Event-Free Survival (EFS)   [ Time Frame: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]

19.  Secondary:   Percentage of Participants Who Died   [ Time Frame: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]

20.  Secondary:   Overall Survival (OS)   [ Time Frame: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]

21.  Secondary:   Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab   [ Time Frame: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18 ]

22.  Secondary:   Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)   [ Time Frame: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18 ]


  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: NCT00950300     History of Changes
Other Study ID Numbers: BO22227
2008-007326-19 ( EudraCT Number )
First Submitted: July 30, 2009
First Posted: July 31, 2009
Results First Submitted: November 4, 2016
Results First Posted: January 23, 2017
Last Update Posted: January 23, 2018