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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Breast International Group
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00553358
First received: November 1, 2007
Last updated: August 15, 2016
Last verified: August 2016
Results First Received: May 26, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   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
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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
Overall Participants Analyzed 
[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 
Number of participants with tumor cells of the indicated histologic grade [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 
[1] Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.
Number of participants with lymph nodes (LNs) of the indicated clinical N stage [1] 
[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 
[1] 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.
Number of participants with the indicated IHC results [1] 
[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 
[1] 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.
Number of participants with the indicated FISH results [1] 
[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] 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) ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Number of Participants With Negative Lymph Nodes at the Time of Surgery
Measure Description Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis.
Time Frame Time of 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. Participants with a lymph node status of pNX (i.e., regional lymph nodes cannot be assessed) were omitted from the analysis of node-negative participants.

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
Participants Analyzed 
[Units: Participants]
 130   134   128 
Number of Participants With Negative Lymph Nodes at the Time of Surgery 
[Units: Participants]
 64   78   91 

No statistical analysis provided for Number of Participants With Negative Lymph Nodes at the Time of Surgery



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

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:   01/2019   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:   08/2021   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:   08/2021   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:   08/2021   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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