History of Changes for Study: NCT00999804

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

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Study Record Versions

Version	Submitted Date	Changes
1	October 21, 2009	None (earliest Version on record)
2	May 25, 2010	Contacts/Locations and Study Status
3	November 2, 2010	Contacts/Locations and Study Status
4	May 2, 2011	Study Status and Contacts/Locations
5	October 27, 2011	Recruitment Status, Contacts/Locations, Sponsor/Collaborators, Study Status, Study Design, Study Description, Conditions, Oversight and Study Identification
6	January 24, 2012	Outcome Measures, Study Status and Study Identification
7	July 24, 2012	Outcome Measures, Study Status and Contacts/Locations
8	March 22, 2013	Study Status, Contacts/Locations and Eligibility
9	November 7, 2013	Study Status
10	May 14, 2014	Study Status
11	July 22, 2014	Recruitment Status, Study Status and Contacts/Locations
12	November 18, 2014	Study Status
13	July 27, 2015	Study Status
14	October 19, 2016	Arms and Interventions, Outcome Measures, Study Status, Study Design, Results and IPDSharing
15	February 2, 2017	Sponsor/Collaborators, Study Status and Outcome Measures
16	January 31, 2019	Study Status
17	July 16, 2020	Study Status and Outcome Measures
18	August 5, 2021	Study Status
19	May 15, 2022	Study Status
20	June 14, 2023	Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	H-25846
Brief Title:	Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy (HEX)
Official Title:	A Neoadjuvant Study of Extended Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2-Overexpressing Breast Cancer Patients
Secondary IDs:

Study Status


Record Verification:	October 2009
Overall Status:	Not yet recruiting
Study Start:	January 2010
Primary Completion:	January 2015 [Anticipated]
Study Completion:	January 2018 [Anticipated]

First Submitted:	October 21, 2009
First Submitted that Met QC Criteria:	October 21, 2009
First Posted:	October 22, 2009 [Estimate]

Last Update Submitted that Met QC Criteria:	October 21, 2009
Last Update Posted:	October 22, 2009 [Estimate]

Sponsor/Collaborators


Sponsor:	Baylor Breast Care Center
Responsible Party:
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	Yes

Study Description

Brief Summary:

Breast cancer cells have certain characteristics or traits--these traits are called biomarkers. There are three biomarkers that help doctors decide which treatment to give any given patient. These biomarkers are the estrogen receptor (ER), progesterone receptor (PgR), and HER2 protein. Breast cancer cells that have a large number of estrogen or progesterone receptors are called ER and/or PgR positive. Cancers that are ER and/or PgR positive use the hormones estrogen and progesterone to help them grow. Not all breast cancers are ER or PgR positive. Patients are being asked to take part in this study that have a special type of breast cancer called HER2 positive breast cancer. HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor-2 (HER2). HER2 is located on the outer surface of a cancer cell. The HER2 protein sends a signal to the inside of the cancer cells telling it to grow and divide.

There are two medications that directly target this HER2 protein. One medication is called trastuzumab(Herceptin), and the other medication is called lapatinib (Tykerb). Both medications are FDA-approved for the treatment of women with HER2+ breast cancer. Each medication attaches to the protein so that it can no longer function. Once the protein stops working, the cancer cells can no longer make copies of themselves. This makes cancer shrink. Both drugs target HER2; however each drug works a little bit differently.

We have found that some patients respond better to Herceptin, and some patients respond better to Tykerb. Right now, we are not sure why some patients respond to one drug but do not respond to the other drug. One possibility is that in some patients, the HER2 protein finds another way to send its message to the inside of the cell (similar to a road detour). For example, when one path is "closed" because the drug is blocking it, the HER2 protein finds a different way to send its signal. We think that we can completely block the HER2 protein by giving patients both Tykerb and Herceptin.

Some patients with HER positive breast cancer are also ER and/or PgR positive. Even after HER2 is completely blocked, these types of cancer cells can still grow by using the estrogen or progesterone receptor. If a patient is told they are ER and/or PgR positive, they will also take an anti-estrogen pill along with Tykerb and Herceptin. We think that we can stop cancer growth more completely by blocking both the HER2 protein and the ER/PR receptors.

Detailed Description:

Conditions


Conditions:	Advanced Breast Cancer
Keywords:	Locally Advanced Breast Cancer Neoadjuvant Endocrine

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Non-Randomized
Enrollment:	55 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Active Comparator: HER2 Positive Patients that are HER2 Positive will be in this Arm	Drug: Herceptin / Lapatinib biologic dosed mg per kg Other Names: Herceptin
Experimental: Endocrine Patients that er ER/PR positive will be in this arm	Drug: Letrozole 2.5 mg Other Names: Femarra, Letrozole

Outcome Measures


Primary Outcome Measures:
1.	The primary endpoint of the study is clinical efficacy, as determined by clinical tumor measurements and pathologic response. [ Time Frame: 5 years ]
Secondary Outcome Measures:
1.	Safety analyses will include summaries of adverse event rates (both frequency and incidence tables), baseline laboratory parameters and changes from baseline, frequency of CTC toxicity grades for both laboratory and non-laboratory data. [ Time Frame: 8 years ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	Female
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: All patients must be female and at least 18 years of age. Signed informed consent. Locally advanced breast cancers are eligible. Locally advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary nodal involvement*. (If tumors are less than 3 cm, we will use the radiologically measured tumor size to determine if the tumor meets the minimal size requirements.) Patients must have histologically confirmed invasive mammary carcinoma that is HER2 overexpressing, defined as 3+ by immunohistochemistry, or a FISH/CEP ratio greater than 2. Negative serum pregnancy test (HCG) within 7 days of starting study drug, if of child-bearing potential. Kidney and liver function tests - all within 1.5 times the institutional upper limit of normal. Performance status (WHO/ECOG scale) 0-1 and life expectancy >6 months. No evidence of brain or leptomeningeal disease, or any other Stage IV disease. No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Exclusion Criteria: Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential. Severe underlying chronic illness or disease. Evidence of distant metastases. Cardiomyopathy or baseline LVEF less than 50%. Other investigational drugs while on study. Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded Taking any lapatinib prohibited medication(s)

Contacts/Locations


Central Contact Person:	Anne Pavlick, BS Telephone: 713-798-1975 Email: acpavlic@bcm.edu
Central Contact Backup:	Amber Froehlich, BA Telephone: 713-798-7814 Email: amberf@bcm.edu
Study Officials:	Jenny Chang, MD Principal Investigator Baylor College of Medicine
Locations:	United States, Texas
	Baylor College of Medicine Lester and Sue Smith Breast Center Houston, Texas, United States, 77030 Contact:Contact: Anne Pavlick, BS 713-798-1975 acpavlic@bcm.edu Contact:Contact: Amber Froehlich, BA 713-798-7814 amberf@bcm.edu Contact:Sub-Investigator: Mothaffar Rimawi, MD Contact:Sub-Investigator: Angel Rodriguez, MD Contact:Sub-Investigator: Heather West, MD Contact:Sub-Investigator: Kent Osborne, MD

IPDSharing


Plan to Share IPD:

References


Links:
Available IPD/Information: