Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy (HELEX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00999804
Recruitment Status : Active, not recruiting
First Posted : October 22, 2009
Results First Posted : December 12, 2016
Last Update Posted : February 19, 2019
Sponsor:
Collaborators:
Translational Breast Cancer Research Consortium
GlaxoSmithKline
Information provided by (Responsible Party):
Mothaffar Rimawi, Baylor Breast Care Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Lapatinib
Drug: Letrozole
Drug: Trastuzumab
Enrollment 128
Recruitment Details Participants were recruited between October 2011 and July 2014 at 10 study sites: Baylor College of Medicine, UAB, University of Chicago, Johns Hopkins, Duke, Indiana University, Vanderbilt, MDACC, DFCI, and Mayo Clinic.
Pre-assignment Details Participants screened up to 28-day period.
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Period Title: Overall Study
Started 85 43
Completed 64 38
Not Completed 21 5
Reason Not Completed
Lack of Efficacy             9             2
Adverse Event             4             3
Withdrawal by Subject             4             0
Death             1             0
Ineligible             3             0
Arm/Group Title 24-week Arm 12-week Arm Total
Hide Arm/Group Description

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Total of all reporting groups
Overall Number of Baseline Participants 85 43 128
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 85 participants 43 participants 128 participants
50
(23 to 80)
57
(38 to 88)
52
(23 to 88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 43 participants 128 participants
Female
85
 100.0%
43
 100.0%
128
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 43 participants 128 participants
Hispanic or Latino
15
  17.6%
9
  20.9%
24
  18.8%
Not Hispanic or Latino
69
  81.2%
33
  76.7%
102
  79.7%
Unknown or Not Reported
1
   1.2%
1
   2.3%
2
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 43 participants 128 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   3.5%
2
   4.7%
5
   3.9%
Native Hawaiian or Other Pacific Islander
1
   1.2%
0
   0.0%
1
   0.8%
Black or African American
11
  12.9%
10
  23.3%
21
  16.4%
White
68
  80.0%
31
  72.1%
99
  77.3%
More than one race
1
   1.2%
0
   0.0%
1
   0.8%
Unknown or Not Reported
1
   1.2%
0
   0.0%
1
   0.8%
1.Primary Outcome
Title Pathologic Complete Response
Hide Description

Pathologic complete response was defined as no residual invasive cancer in the breast, after 12 or 24 weeks of lapatinib/trastuzumab with or without endocrine therapy.

This outcome is based on patient's pathological report. We are not measuring the clinical response.

Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable.

Time Frame 12 or 24 week depending the arm assignment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participant were not evaluable: 3 participant were found ineligible for the study and one participant died before surgery.
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description:

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Overall Number of Participants Analyzed 81 43
Measure Type: Number
Unit of Measure: participants
pathologic complete response 20 5
non-complete pathologic response 61 38
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 24-week Arm
Comments

The study was planned to enroll 136 patients if the original cohort (n=90) was deemed successful. The 24 weeks arm ran as a single arm, using an admissible Simon-like two-stage design. The 12 weeks arm accrued as long as the 24 weeks arm is open.

The analysis of the first cohort indicated that 15 pCR were observed , which did not meet the required 20 or more responses. The accrual was closed early and the study has a total of 128 participants.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion of pCR
Estimated Value 0.25
Estimation Comments No comparison is required between the 24 weeks arm and 12 weeks arm. The study is designed as the 24 weeks arm ran as a single arm, using an admissible Simon-like two-stage design and required 20 or more responses in the first 55 evaluable patients.
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy
Time Frame 12 week or 24 weeks depending on arm assignment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who started the study treatment will be evaluable for safety analysis
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description:

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Overall Number of Participants Analyzed 85 43
Measure Type: Number
Unit of Measure: participants
61 26
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 24-week Arm
Comments This outcome is to establish the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy. No comparison between the 2 arms is required.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion of patients with AE
Estimated Value 0.72
Estimation Comments 61 out of 85 patients (72%) in the 24-week arm had at least 1 adverse events.
3.Secondary Outcome
Title Total Pathologic Complete Response
Hide Description pathologic complete response was defined as no residual invasive cancer in the breast and the axillary lymph nodes.
Time Frame 12 weeks or 24 weeks depending on arm assignment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participant were not evaluable: 3 participant were found ineligible for the study and one participant died before surgery.
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description:

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Overall Number of Participants Analyzed 81 43
Measure Type: Number
Unit of Measure: participants
total complete pathologic response 8 2
not total complete pathologic response 72 41
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 24-week Arm
Comments No comparison between the two arms is required.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion of tpCR in 24 weeks arm
Estimated Value 0.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Response
Hide Description [Not Specified]
Time Frame 12 weeks or 24 weeks depending on arm assignment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participants were not evaluable for efficacy.
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description:

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Overall Number of Participants Analyzed 81 43
Measure Type: Number
Unit of Measure: participants
Complete response 46 21
Partial response 10 13
Stable disease 2 3
Progressive disease 13 4
Unknown 10 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 24-week Arm
Comments No comparison between the 2 arm is required for this study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter proportion of CR+PR in 24 weeks arm
Estimated Value 0.69
Estimation Comments [Not Specified]
Time Frame 7 months
Adverse Event Reporting Description Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
 
Arm/Group Title 24-week Arm 12-week Arm
Hide Arm/Group Description

Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.

Lapatinib: 1000 mg by mouth daily

Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only)

Trastuzumab: 6 mg/kg intravenously, every 3 weeks

All-Cause Mortality
24-week Arm 12-week Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
24-week Arm 12-week Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/85 (3.53%)      1/43 (2.33%)    
Cardiac disorders     
Cardiac arrest  1  1/85 (1.18%)  1 0/43 (0.00%)  0
Hepatobiliary disorders     
Elevated AST  1  1/85 (1.18%)  1 0/43 (0.00%)  0
Infections and infestations     
Breast infection  1  1/85 (1.18%)  1 0/43 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  0/85 (0.00%)  0 1/43 (2.33%)  1
Hematuria  1  0/85 (0.00%)  0 1/43 (2.33%)  1
Renal calculi  1  0/85 (0.00%)  0 1/43 (2.33%)  1
Urinary retention  1  0/85 (0.00%)  0 1/43 (2.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
24-week Arm 12-week Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   61/85 (71.76%)      26/43 (60.47%)    
Blood and lymphatic system disorders     
Anemia  1  8/85 (9.41%)  16 4/43 (9.30%)  11
Gastrointestinal disorders     
Diarrhea  1  30/85 (35.29%)  51 14/43 (32.56%)  22
Mucositis oral  1  9/85 (10.59%)  15 10/43 (23.26%)  10
Vomiting  1  6/85 (7.06%)  11 2/43 (4.65%)  2
General disorders     
Fatigue  1  14/85 (16.47%)  19 8/43 (18.60%)  8
Nusea  1  11/85 (12.94%)  15 6/43 (13.95%)  6
Pain  1  5/85 (5.88%)  6 2/43 (4.65%)  2
Investigations     
Alanine aminotransferase increased  1  22/85 (25.88%)  54 5/43 (11.63%)  7
Alkaline phosphatase increased  1  12/85 (14.12%)  17 3/43 (6.98%)  3
Aspartate aminotransferase increased  1  23/85 (27.06%)  46 7/43 (16.28%)  7
Blood bilirubin increased  1  8/85 (9.41%)  15 0/43 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia  1  8/85 (9.41%)  10 3/43 (6.98%)  3
Nervous system disorders     
Dysgeusia  1  4/85 (4.71%)  4 4/43 (9.30%)  4
Headache  1  5/85 (5.88%)  5 2/43 (4.65%)  2
Psychiatric disorders     
Anxiety  1  4/85 (4.71%)  4 3/43 (6.98%)  3
Insomnia  1  7/85 (8.24%)  7 4/43 (9.30%)  4
Skin and subcutaneous tissue disorders     
Alopecia  1  3/85 (3.53%)  3 4/43 (9.30%)  4
Dry skin  1  8/85 (9.41%)  9 2/43 (4.65%)  2
Pruritus  1  5/85 (5.88%)  5 3/43 (6.98%)  3
Rash acneiform  1  17/85 (20.00%)  22 5/43 (11.63%)  5
Vascular disorders     
Hot flashes  1  8/85 (9.41%)  8 4/43 (9.30%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mothaffar Rimawi
Organization: Baylor College of Medicine
Phone: 7137981311
EMail: rimawi@bcm.edu
Layout table for additonal information
Responsible Party: Mothaffar Rimawi, Baylor Breast Care Center
ClinicalTrials.gov Identifier: NCT00999804     History of Changes
Other Study ID Numbers: H-25846
First Submitted: October 21, 2009
First Posted: October 22, 2009
Results First Submitted: December 29, 2015
Results First Posted: December 12, 2016
Last Update Posted: February 19, 2019