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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: February 14, 2013
Last verified: February 2013
History of Changes
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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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  
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  
Number of participants with lymph nodes (LNs) of the indicated clinical N stage [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  
Number of participants with the indicated IHC results [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  
Number of participants with the indicated FISH results [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 ]
  Show Outcome Measure 1

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

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

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

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

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) ]
  Show Outcome Measure 6

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

8.  Secondary:   Overall Survival   [ Time Frame: Following surgery, every 12 months until Year 10 ]
Results not yet posted.   Anticipated Posting 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 posted.   Anticipated Posting 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 posted.   Anticipated Posting 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 posted.   Anticipated Posting 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 posted.   Anticipated Posting Date:   01/2013   Safety Issue:   No


  Serious Adverse Events
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  Other Adverse Events
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Time Frame No text entered.
Additional Description Only events, assessments, and treatments with a start date on or before the end date of the neoadjuvant phase have been summarized. One non-serious event was reported as an uncoded event. A non-serious event of dental care was actually coded to "Surgical and medical procedures."

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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

Other Adverse Events
    Lapatinib 1500 mg     Trastuzumab 2 mg/kg     Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg  
Total, other (not including serious) adverse events        
# participants affected / at risk     143/154     123/149     138/152  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     24/154 (15.58%)     19/149 (12.75%)     34/152 (22.37%)  
Neutropenia † 1      
# participants affected / at risk     34/154 (22.08%)     10/149 (6.71%)     25/152 (16.45%)  
Leukopenia † 1      
# participants affected / at risk     10/154 (6.49%)     5/149 (3.36%)     9/152 (5.92%)  
Gastrointestinal disorders        
Diarrhoea † 1      
# participants affected / at risk     118/154 (76.62%)     39/149 (26.17%)     117/152 (76.97%)  
Nausea † 1      
# participants affected / at risk     56/154 (36.36%)     32/149 (21.48%)     42/152 (27.63%)  
Vomiting † 1      
# participants affected / at risk     29/154 (18.83%)     12/149 (8.05%)     29/152 (19.08%)  
Abdominal pain † 1      
# participants affected / at risk     25/154 (16.23%)     8/149 (5.37%)     18/152 (11.84%)  
Stomatitis † 1      
# participants affected / at risk     15/154 (9.74%)     12/149 (8.05%)     22/152 (14.47%)  
Abdominal pain upper † 1      
# participants affected / at risk     19/154 (12.34%)     11/149 (7.38%)     15/152 (9.87%)  
Dyspepsia † 1      
# participants affected / at risk     20/154 (12.99%)     7/149 (4.70%)     12/152 (7.89%)  
Constipation † 1      
# participants affected / at risk     9/154 (5.84%)     10/149 (6.71%)     5/152 (3.29%)  
Abdominal distension † 1      
# participants affected / at risk     8/154 (5.19%)     5/149 (3.36%)     9/152 (5.92%)  
Haemorrhoids † 1      
# participants affected / at risk     9/154 (5.84%)     4/149 (2.68%)     6/152 (3.95%)  
Mouth ulceration † 1      
# participants affected / at risk     0/154 (0.00%)     1/149 (0.67%)     8/152 (5.26%)  
General disorders        
Asthenia † 1      
# participants affected / at risk     45/154 (29.22%)     27/149 (18.12%)     31/152 (20.39%)  
Fatigue † 1      
# participants affected / at risk     33/154 (21.43%)     26/149 (17.45%)     36/152 (23.68%)  
Mucosal inflammation † 1      
# participants affected / at risk     29/154 (18.83%)     15/149 (10.07%)     24/152 (15.79%)  
Pyrexia † 1      
# participants affected / at risk     13/154 (8.44%)     17/149 (11.41%)     23/152 (15.13%)  
Chills † 1      
# participants affected / at risk     1/154 (0.65%)     4/149 (2.68%)     9/152 (5.92%)  
Hepatobiliary disorders        
Hypertransaminasaemia † 1      
# participants affected / at risk     46/154 (29.87%)     32/149 (21.48%)     46/152 (30.26%)  
Hyperbilirubinaemia † 1      
# participants affected / at risk     21/154 (13.64%)     4/149 (2.68%)     19/152 (12.50%)  
Infections and infestations        
Nasopharyngitis † 1      
# participants affected / at risk     11/154 (7.14%)     7/149 (4.70%)     8/152 (5.26%)  
Urinary tract infection † 1      
# participants affected / at risk     11/154 (7.14%)     4/149 (2.68%)     5/152 (3.29%)  
Paronychia † 1      
# participants affected / at risk     2/154 (1.30%)     0/149 (0.00%)     10/152 (6.58%)  
Investigations        
Weight decreased † 1      
# participants affected / at risk     9/154 (5.84%)     0/149 (0.00%)     6/152 (3.95%)  
Metabolism and nutrition disorders        
Decreased appetite † 1      
# participants affected / at risk     34/154 (22.08%)     10/149 (6.71%)     30/152 (19.74%)  
Hyperphosphatasaemia † 1      
# participants affected / at risk     16/154 (10.39%)     8/149 (5.37%)     16/152 (10.53%)  
Musculoskeletal and connective tissue disorders        
Myalgia † 1      
# participants affected / at risk     27/154 (17.53%)     25/149 (16.78%)     24/152 (15.79%)  
Arthralgia † 1      
# participants affected / at risk     13/154 (8.44%)     13/149 (8.72%)     9/152 (5.92%)  
Musculoskeletal pain † 1      
# participants affected / at risk     11/154 (7.14%)     5/149 (3.36%)     4/152 (2.63%)  
Back pain † 1      
# participants affected / at risk     4/154 (2.60%)     6/149 (4.03%)     9/152 (5.92%)  
Nervous system disorders        
Headache † 1      
# participants affected / at risk     14/154 (9.09%)     22/149 (14.77%)     16/152 (10.53%)  
Neuropathy peripheral † 1      
# participants affected / at risk     15/154 (9.74%)     17/149 (11.41%)     14/152 (9.21%)  
Paraesthesia † 1      
# participants affected / at risk     9/154 (5.84%)     14/149 (9.40%)     19/152 (12.50%)  
Peripheral sensory neuropathy † 1      
# participants affected / at risk     14/154 (9.09%)     12/149 (8.05%)     9/152 (5.92%)  
Dizziness † 1      
# participants affected / at risk     11/154 (7.14%)     11/149 (7.38%)     7/152 (4.61%)  
Hypoaesthesia † 1      
# participants affected / at risk     6/154 (3.90%)     9/149 (6.04%)     9/152 (5.92%)  
Dysgeusia † 1      
# participants affected / at risk     11/154 (7.14%)     1/149 (0.67%)     11/152 (7.24%)  
Psychiatric disorders        
Insomnia † 1      
# participants affected / at risk     15/154 (9.74%)     16/149 (10.74%)     17/152 (11.18%)  
Renal and urinary disorders        
Dysuria † 1      
# participants affected / at risk     3/154 (1.95%)     1/149 (0.67%)     9/152 (5.92%)  
Reproductive system and breast disorders        
Breast pain † 1      
# participants affected / at risk     3/154 (1.95%)     9/149 (6.04%)     2/152 (1.32%)  
Respiratory, thoracic and mediastinal disorders        
Epistaxis † 1      
# participants affected / at risk     28/154 (18.18%)     21/149 (14.09%)     29/152 (19.08%)  
Cough † 1      
# participants affected / at risk     12/154 (7.79%)     17/149 (11.41%)     14/152 (9.21%)  
Oropharyngeal pain † 1      
# participants affected / at risk     15/154 (9.74%)     8/149 (5.37%)     8/152 (5.26%)  
Dyspnoea † 1      
# participants affected / at risk     9/154 (5.84%)     6/149 (4.03%)     9/152 (5.92%)  
Rhinorrhoea † 1      
# participants affected / at risk     4/154 (2.60%)     8/149 (5.37%)     9/152 (5.92%)  
Skin and subcutaneous tissue disorders        
Alopecia † 1      
# participants affected / at risk     75/154 (48.70%)     75/149 (50.34%)     79/152 (51.97%)  
Rash † 1      
# participants affected / at risk     59/154 (38.31%)     19/149 (12.75%)     57/152 (37.50%)  
Nail disorder † 1      
# participants affected / at risk     15/154 (9.74%)     8/149 (5.37%)     24/152 (15.79%)  
Dry skin † 1      
# participants affected / at risk     21/154 (13.64%)     4/149 (2.68%)     19/152 (12.50%)  
Acne † 1      
# participants affected / at risk     20/154 (12.99%)     3/149 (2.01%)     17/152 (11.18%)  
Pruritus † 1      
# participants affected / at risk     19/154 (12.34%)     4/149 (2.68%)     17/152 (11.18%)  
Dermatitis acneiform † 1      
# participants affected / at risk     10/154 (6.49%)     4/149 (2.68%)     11/152 (7.24%)  
Erythema † 1      
# participants affected / at risk     10/154 (6.49%)     4/149 (2.68%)     9/152 (5.92%)  
Skin fissures † 1      
# participants affected / at risk     2/154 (1.30%)     4/149 (2.68%)     10/152 (6.58%)  
Palmar-Plantar erythrodysaesthesia syndrome † 1      
# participants affected / at risk     5/154 (3.25%)     1/149 (0.67%)     8/152 (5.26%)  
Vascular disorders        
Hot flush † 1      
# participants affected / at risk     7/154 (4.55%)     4/149 (2.68%)     9/152 (5.92%)  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



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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.


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.  


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: NCT00553358     History of Changes
Other Study ID Numbers: EGF106903
Study First Received: November 1, 2007
Results First Received: May 26, 2011
Last Updated: February 14, 2013
Health Authority: Spain: Ministry of Health
Lithuania: State Medicine Control Agency - Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency