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A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01641939
First received: July 13, 2012
Last updated: June 30, 2016
Last verified: June 2016
Results First Received: June 30, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Gastric Cancer
Interventions: Drug: Taxane
Drug: trastuzumab emtansine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 415 participants were randomized, of these 111 participants in taxane arm, 224 participants in 2.4 milligram per kilogram (mg/kg) trastuzumab emtansine arm (across both phase 2 and 3), and 69 participants (phase 2-dose selection portion of the study) in 3.6 mg/kg trastuzumab emtansine arm received at least one dose of the treatment.

Reporting Groups
  Description
Standard Taxane Therapy Docetaxel was administered at 75 milligram per meter square (mg/m^2) intravenously (IV) on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab Emtansine 2.4 mg Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab Emtansine 3.6 mg Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.

Participant Flow:   Overall Study
    Standard Taxane Therapy   Trastuzumab Emtansine 2.4 mg   Trastuzumab Emtansine 3.6 mg
STARTED   117   228   70 
Phase 2   37   75   70 
Phase 3   80   153   0 
COMPLETED   0   0   0 
NOT COMPLETED   117   228   70 
Death                72                164                54 
Lost to Follow-up                2                2                1 
Withdrawal by Subject                14                11                4 
On treatment                1                7                2 
In follow-up                28                44                9 



  Baseline Characteristics
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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) analysis population included all randomized participants; participants grouped according to the therapy they were randomized to receive.

Reporting Groups
  Description
Standard Taxane Therapy Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab Emtansine 2.4 mg Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab Emtansine 3.6 mg Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Total Total of all reporting groups

Baseline Measures
   Standard Taxane Therapy   Trastuzumab Emtansine 2.4 mg   Trastuzumab Emtansine 3.6 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 117   228   70   415 
Age 
[Units: Years]
Mean (Standard Deviation)
 62.1  (10.3)   60.5  (10.9)   61.2  (11.4)   61.1  (10.8) 
Gender 
[Units: Participants]
       
Female   22   51   17   90 
Male   95   177   53   325 


  Outcome Measures
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1.  Primary:   Overall Survival (OS) - Phase 3   [ Time Frame: Date of randomization until death (up to 2 years 3 months) ]

2.  Primary:   Overall Survival (OS) - Phase 2 (Dose Selection Portion of the Study)   [ Time Frame: Date of randomization until death (up to 1 year) ]

3.  Secondary:   Percentage of Participants With Disease Progression or Death According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3   [ Time Frame: Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) ]

4.  Secondary:   Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3   [ Time Frame: Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) ]

5.  Secondary:   Percentage of Participants With Objective Response According to mRECIST v1.1 - Phase 3   [ Time Frame: Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) ]

6.  Secondary:   Duration of Objective Response (DOR) - Phase 3   [ Time Frame: Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) ]

7.  Secondary:   Percentage of Participants With Clinically Significant Improvement in European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC QLQ-C30) Score - Phase 3   [ Time Frame: Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at follow-up (up to 2 years 3 months) ]

8.  Secondary:   Percentage of Participants With Clinically Significant Improvement in Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) Score - Phase 3   [ Time Frame: Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months) ]

9.  Secondary:   Percentage of Participants With Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3   [ Time Frame: Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months) ]

10.  Secondary:   Time to Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3   [ Time Frame: Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months) ]

11.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 1   [ Time Frame: Day 1 (D1) of Cycle 1 (C1) and C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]

12.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) - Stage 1   [ Time Frame: C1D1 and C1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]

13.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 2   [ Time Frame: C1D1; C4D1 ]

14.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] - Stage 1   [ Time Frame: D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]

15.  Secondary:   Plasma Decay Half-Life (t1/2) - Stage 1   [ Time Frame: D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]

16.  Secondary:   Volume of Distribution at Steady State (Vss) - Stage 1   [ Time Frame: D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]

17.  Secondary:   Systemic Clearance (CL) - Stage 1   [ Time Frame: D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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-LaRoche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01641939     History of Changes
Other Study ID Numbers: BO27952
2012-000660-22 ( EudraCT Number )
Study First Received: July 13, 2012
Results First Received: June 30, 2016
Last Updated: June 30, 2016
Health Authority: United States: Food and Drug Administration