Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Breast International Group
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00553358
First received: November 1, 2007
Last updated: September 18, 2014
Last verified: September 2014
Results First Received: May 26, 2011  
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
Drug: Paclitaxel

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Lapatinib 1500 mg Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks
Trastuzumab 2 mg/kg Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks

Participant Flow:   Overall Study
    Lapatinib 1500 mg     Trastuzumab 2 mg/kg     Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg  
STARTED     154     149     152  
COMPLETED     101     137     92  
NOT COMPLETED     53     12     60  
Adverse Event                 29                 2                 32  
Lost to Follow-up                 0                 0                 1  
Protocol Violation                 0                 1                 1  
Withdrawal by Subject                 5                 0                 1  
Recurrence of Disease                 3                 4                 1  
Participant Withdrawal from Drug                 0                 0                 3  
Missing                 1                 1                 1  
Other: Reason Not Specified                 15                 4                 20  



  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 1500 mg Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks
Trastuzumab 2 mg/kg Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Total Total of all reporting groups

Baseline Measures
    Lapatinib 1500 mg     Trastuzumab 2 mg/kg     Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg     Total  
Number of Participants  
[units: participants]
  154     149     152     455  
Age  
[units: Years]
Median ( Full Range )
  50.0  
  ( 28 to 79 )  
  49.0  
  ( 23 to 77 )  
  50.0  
  ( 25 to 80 )  
  50.0  
  ( 23 to 80 )  
Gender  
[units: Participants]
       
Female     154     149     152     455  
Male     0     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
       
American Indian or Alaska Native     13     14     15     42  
Asian - Central/South     7     5     5     17  
Asian - East     30     28     31     89  
Asian - South East     0     0     2     2  
Black or African American/African Heritage     0     4     4     8  
White - Arabic/North African Heritage     6     5     3     14  
White - Caucasian European Heritage     97     93     92     282  
Missing     1     0     0     1  
Study-Specific Measure [1]
[units: participants]
       
Well differentiated     2     5     5     12  
Moderately differentiated     56     53     63     172  
Poorly differentiated     73     68     64     205  
Differentiation cannot be assessed     22     23     20     65  
Missing     1     0     0     1  
Study-Specific Measure [2]
[units: participants]
       
N0     34     41     48     123  
N1     95     85     80     260  
N2 (including N2a and N2b)     19     13     15     47  
N3 (including N3a, N3b, and N3c)     6     7     6     19  
Nx     0     3     3     6  
Study-Specific Measure [3]
[units: participants]
       
Not applicable     60     53     61     174  
Equivocal: Score of 2+     9     5     8     22  
Positive: Score of 3+     81     89     76     246  
Negative: Score of 0-1+     0     1     3     4  
Non interpretable     4     1     4     9  
Study-Specific Measure [4]
[units: participants]
       
Not applicable     38     42     41     121  
Amplified     115     105     109     329  
Not amplified     1     2     1     4  
Not interpretable     0     0     1     1  
[1] Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.
[2] Clinical N stage is an evaluation/staging of LN status through physical examination. N0, no regional LN metastasis; N1, metastasis to movable ipsilateral axillary LNs (IALNs); N2a, metastasis in IALNs fixed to one another (matted) or the other structures; N2b, metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary LN metastasis; N3a, metastasis in ipsilateral infraclavicular LNs; N3b, metastasis in ipsilateral internal mammary LNs fixed and axillary LN; N3c, metastasis in ipsilateral subclavicar LNs; Nx, not assessed.
[3] An Immunohistochemistry (IHC) test gives a score of 0 to 3+, which indicates the amount of Human Epidermal Growth Factor (HER2) receptor proteins on the cancer cells in the sample tissue. A positive score (3+) indicates that HER2 receptor protein is present, a negative score (0-1+) indicates that no HER2 receptor protein is present, and an equivocal score (2+) indicates uncertainty and a result that is open for interpretation. Equivocal results require additional testing. “Not applicable” refers to the number of participants who did not have IHC testing done.
[4] The Fluorescent In Situ Hybridization (FISH) assay was used to determine the overexpression and/or amplification of HER2 in the invasive component of the primary tumor. Amplified indicates that the cell is overexpressing copies of the HER2 gene. Not amplified indicates that there is no overexpression of copies of the HER2 gene. “Not applicable” refers to the number of participants who did not have the FISH assay performed.



  Outcome Measures
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1.  Primary:   Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery   [ Time Frame: Weeks 20 to 22 ]

2.  Secondary:   Number of Participants With Overall Response at Week 6   [ Time Frame: Week 6 ]

3.  Secondary:   Number of Participants With Overall Response at the Time of Surgery   [ Time Frame: Time of surgery (Weeks 20 to 22) ]

4.  Secondary:   Number of Participants With Negative Lymph Nodes at the Time of Surgery   [ Time Frame: Time of surgery (Weeks 20 to 22) ]

5.  Secondary:   Number of Participants With Actual Indicated Surgery   [ Time Frame: At surgery (Weeks 20 to 22) ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Number of Participants With Actual Indicated Surgery
Measure Description Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadranectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable.
Time Frame At surgery (Weeks 20 to 22)  
Safety Issue No  

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.
ITT Population

Reporting Groups
  Description
Lapatinib 1500 mg Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab 2 mg/kg Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks

Measured Values
    Lapatinib 1500 mg     Trastuzumab 2 mg/kg     Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg  
Number of Participants Analyzed  
[units: participants]
  154     149     152  
Number of Participants With Actual Indicated Surgery  
[units: participants]
     
Conservative     66     58     63  
Non-conservative     77     85     80  
Non-operable     11     6     9  

No statistical analysis provided for Number of Participants With Actual Indicated Surgery



6.  Secondary:   Estimate of Treatment Contrast for Change From Baseline in Tumor Size at Week 6 and at Surgery   [ Time Frame: Week 6 and surgery (Weeks 20 to 22) ]

7.  Secondary:   Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab   [ Time Frame: Week 6 ]

8.  Secondary:   Overall Survival   [ Time Frame: Following surgery, every 12 months until Year 10 ]
Results not yet reported.   Anticipated Reporting Date:   01/2020   Safety Issue:   No

9.  Secondary:   Disease-free Survival (DFS)   [ Time Frame: Following surgery, every 12 months until Year 10 ]
Results not yet reported.   Anticipated Reporting Date:   08/2013   Safety Issue:   No

10.  Secondary:   Number of Participants With Metabolic Response of Complete Response (mCR), Partial Response (mPR), or Stable Disease (mSD) as Determined by Positron Emission Tomography/Computed Tomography (PET/CT)   [ Time Frame: Baseline, Week 2, and Week 6 ]
Results not yet reported.   Anticipated Reporting Date:   12/2011   Safety Issue:   No

11.  Secondary:   Number of Participants With the Indicated Biomarker Expression   [ Time Frame: Baseline, Week 2, and at surgery (Weeks 20 to 22) ]
Results not yet reported.   Anticipated Reporting Date:   01/2013   Safety Issue:   No

12.  Secondary:   Number of Circulating Tumor Cells (CTC) in the Bloodstream   [ Time Frame: Baseline, Week 2 of neo-adjuvant phase (Weeks 1-34), at surgery (Weeks 20 to 22), Week 10 of adjuvant phase, 6 months after completion of adjuvant treatment, and at recurrence ]
Results not yet reported.   Anticipated Reporting Date:   01/2013   Safety Issue:   No


  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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