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

• ClinicalTrials.gov Identifier: NCT00999804
• Recruitment Status: Active, not recruiting
• First Posted: October 22, 2009
• Results First Posted: December 12, 2016
• Last Update Posted: June 18, 2023
• Sponsor: Baylor Breast Care Center
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		24-week Arm	12-week Arm	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response
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

Outcome Measure Data

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
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

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 (legacy)
	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
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

Outcome Measure Data

Analysis Population Description

Participants who started the study treatment will be evaluable for safety analysis

Arm/Group Title	24-week Arm	12-week Arm
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

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 (legacy)
	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
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

Outcome Measure Data

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
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

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 (legacy)
	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
Description	[Not Specified]
Time Frame	12 weeks or 24 weeks depending on arm assignment

Outcome Measure Data

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
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

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 (legacy)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	proportion of CR+PR in 24 weeks arm
	Estimated Value	0.69
	Estimation Comments	[Not Specified]

Adverse Events

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
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	--/--		--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Dr. Mothaffar Rimawi
• Organization: Baylor College of Medicine
• Phone: 7137981311
• EMail: rimawi@bcm.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rimawi MF, Niravath P, Wang T, Rexer BN, Forero A, Wolff AC, Nanda R, Storniolo AM, Krop I, Goetz MP, Nangia JR, Jiralerspong S, Pavlick A, Veeraraghavan J, De Angelis C, Gutierrez C, Schiff R, Hilsenbeck SG, Osborne CK; Translational Breast Cancer Research Consortium. TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer. Clin Cancer Res. 2020 Feb 15;26(4):821-827. doi: 10.1158/1078-0432.CCR-19-0851. Epub 2019 Oct 29.

• Responsible Party: Mothaffar Rimawi, Baylor Breast Care Center
• ClinicalTrials.gov Identifier: NCT00999804
• 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: June 18, 2023