ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Breast International Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00490139
First received: June 20, 2007
Last updated: September 29, 2014
Last verified: September 2014
Results First Received: July 30, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms, Breast
Interventions: Drug: Lapatinib
Biological: Trastuzumab

  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
Treatments administered differed per timing/type of adjuvant chemotherapy. Design (D) 1: (neo) adjuvant anthracycline-based chemotherapy (AABC) prior to targeted therapy (TT); Design 2: TT concurrently with paclitaxel or docetaxel, after completion of a (neo) AABC; Design 2B: TT concurrently with chemotherapy with docetaxel and carboplatin.

Reporting Groups
  Description
Lapatinib plusTrastuzumab Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Trastuzumab Followed by Lapatinib Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Lapatinib Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Trastuzumab Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.

Participant Flow:   Overall Study
    Lapatinib plusTrastuzumab     Trastuzumab Followed by Lapatinib     Lapatinib     Trastuzumab  
STARTED     2093     2091     2100     2097  
COMPLETED     1785     1816     1666     1790  
NOT COMPLETED     308     275     434     307  
Death                 106                 119                 168                 135  
Lost to Follow-up                 56                 46                 58                 56  
Participant Withdrew Consent                 146                 110                 208                 116  



  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.
No text entered.

Reporting Groups
  Description
Lapatinib plusTrastuzumab Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Trastuzumab Followed by Lapatinib Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Lapatinib Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Trastuzumab Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Total Total of all reporting groups

Baseline Measures
    Lapatinib plusTrastuzumab     Trastuzumab Followed by Lapatinib     Lapatinib     Trastuzumab     Total  
Number of Participants  
[units: participants]
  2093     2091     2100     2097     8381  
Age  
[units: years]
Mean ± Standard Deviation
  50.9  ± 10.23     50.8  ± 10.32     51.2  ± 10.18     51.0  ± 10.25     51.0  ± 10.24  
Gender  
[units: participants]
         
Female     2091     2086     2098     2097     8372  
Male     2     5     2     0     9  
Race/Ethnicity, Customized  
[units: participants]
         
American Indian or Alaska Native     48     45     47     47     187  
Asian: Central/South     107     103     110     109     429  
Asian: East     311     312     299     314     1236  
Asian: Japanese     33     36     33     43     145  
Asian: South East     95     92     107     89     383  
Black or African American     38     30     43     25     136  
Native Hawaiian (NH) or Other Pacific     2     4     4     5     15  
White: Arabic     53     52     62     69     236  
White: Caucasian     1392     1402     1372     1382     5548  
Mixed Race/Ancestry     5     7     10     3     25  
Hispanic     2     1     1     3     7  
Mestizo     1     1     3     0     5  
Mauritius Islander     0     0     0     1     1  
Coloured     1     0     1     0     2  
NH and White (Arabic/North African Heritage [HER])     0     0     1     0     1  
European Heritage and South American     1     0     0     0     1  
South American, African HER and European HER     0     1     0     0     1  
Afrikaans-South Africa     1     0     0     0     1  
White South African     0     0     0     1     1  
White South American     1     0     2     0     3  
Southeast and Northeast of South America     0     0     1     0     1  
Mulatto     0     1     0     0     1  
South American Latin American and European HER     0     1     0     0     1  
Black from South America     1     0     0     0     1  
Northeast of South America and European HER     0     0     1     0     1  
Asian (East), NH or Other Pacific Islander     0     0     0     1     1  
Peruvian     0     0     0     1     1  
Mexican     0     0     0     1     1  
American Indian or Alaska Native and White     0     0     1     0     1  
Caucasian and Guamanian (Chamorro)     0     0     1     0     1  
Unknown/Missing     1     3     1     3     8  



  Outcome Measures
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1.  Primary:   Disease-free Survival (DFS)   [ Time Frame: From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization until death due to any cause (median follow-up of 4.5 years) ]

3.  Secondary:   Time to Recurrence   [ Time Frame: From randomization until the date of the first occurrence of a disease recurrence (median follow-up of 4.5 years) ]

4.  Secondary:   Time to Distant Recurrence   [ Time Frame: From randomization until the date of the first occurrence of distant recurrence (median follow-up of 4.5 years) ]

5.  Secondary:   Time to Central Nervous System Recurrence   [ Time Frame: From randomization until the first central nervous system recurrence (median follow-up of 4.5 years) ]

6.  Secondary:   DFS Ignoring Non-breast Second Primary Malignancies   [ Time Frame: From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years) ]


  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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00490139     History of Changes
Obsolete Identifiers: NCT00609024
Other Study ID Numbers: EGF106708
Study First Received: June 20, 2007
Results First Received: July 30, 2014
Last Updated: September 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration