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Breast CancerPhase 2HELEXNCT00999804

Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy

A Phase 2 study testing Lapatinib, Letrozole and Trastuzumab in people with Breast Cancer, run by Baylor Breast Care Center at 8 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Breast cancer is the most common malignancy in the U.S. Targeted therapies such as tamoxifen have been revolutionary in reducing tumor recurrences and mortality in early breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Lapatinib, Letrozole and Trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
128 participants
Where
8 sitesUnited States
Study dates
Oct 2011to Jan 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • Patients with bilateral breast cancer.
  • Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
  • Severe underlying chronic illness or disease.
  • 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.
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  • 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)
  • Inability or unwillingness to comply with, or follow study procedures.
  • Patients who have received any form of treatment for breast cancer within the past five years, including surgical resection, chemotherapy, endocrine therapy, or biologic therapy.
  • Patients with a prior history of ipsilateral invasive breast cancer or carcinoma in situ who present with a new primary.
  • Patients with known active, infectious Hepatitis B, Hepatitis C, or HIV.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • Johns Hopkins

    Baltimore, Maryland, 21231

  • University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02130

  • University of Chicago

    Chicago, Illinois, 60637

  • Duke University

    Durham, North Carolina, 27705

  • Baylor College of Medicine Lester and Sue Smith Breast Center

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

Other trials in United States

About this study

Official title: TBCRC 023: A Randomized Multicenter Phase II Neoadjuvant Trial of Lapatinib Pus Trastuzumab, With or Without Endocrine Therapy for 12 Weeks vs. 24 Weeks in Patients With HER2 Overexpressing Breast Cancer

Breast cancer is the most common malignancy in the U.S. Targeted therapies such as tamoxifen have been revolutionary in reducing tumor recurrences and mortality in early breast cancer. Using this successful paradigm, there has been a continued search for other targeted biologic therapies directed at receptors with known potential for promoting tumor growth.

The estrogen receptor (ER) and/or the HER signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Molecular targets of these pathways provide the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment, and understanding the molecular pathways responsible for this resistance would enable the discovery of new strategies to overcome it.

The superiority of multi-drug HER2-targeted therapy over single agent therapy has been demonstrated in the preclinical setting using mouse xenografts. Trastuzumab, pertuzumab, lapatinib, and gefitinib, represent a group of therapeutic agents that target the HER family by different molecular mechanisms. Used as single agents in the MCF7/HER2-18 xenograft model, these drugs restored or enhanced sensitivity to tamoxifen. However, tumor growth inhibition lasted only 2-3 months before resistance to treatments occurred. However, when gefitinib, a HER1 inhibitor, was added to the two-antibody (T+P) regimen to block signals from HER1 dimers, a complete disappearance of nearly all xenograft tumors was observed; moreover, there was evidence of complete tumor eradication in 50% of the mice. The combination of lapatinib + trastuzumab was also highly effective in eradication of tumor burden, with no evidence of re-growth after 200 days. These xenograft models demonstrate that multi-drug HER2-targeted therapy more effectively induces apoptosis and inhibits proliferation, thereby resulting in tumor regression. Furthermore, HER2 combination therapy appears to more effectively reduce levels of phosphorylated pAKT and MAPK, thus resulting in sustained tumor inhibition.

Read the detailed description

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.

Two medications that directly target this HER2 protein. One is called trastuzumab(Herceptin), and the other 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.

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.

Conditions
Breast Cancer
Being tested
Lapatinib, Letrozole, Trastuzumab
Keywords
Locally Advanced Breast Cancer Neoadjuvant Endocrine
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

    Also called TyKerb

    1000 mg of Lapatinib by mouth daily

  • LetrozoleDrug

    Also called Femara

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

  • TrastuzumabDrug

    Also called Herceptin

    6 mg/kg intravenously, every 3 weeks

Study groups in NCT00999804
Study groupRoleWhat they receive
24-week armExperimentalParticipants 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.
Receives: Drug: Lapatinib; Drug: Letrozole; Drug: Trastuzumab
12-week armActive comparatorParticipants 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.
Receives: Drug: Lapatinib; Drug: Letrozole; Drug: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response

    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.

    Measured: 12 or 24 week depending the arm assignment

Secondary outcomes (3)
  1. Number of Participants With Adverse Events

    the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy

    Measured: 12 week or 24 weeks depending on arm assignment

  2. Total Pathologic Complete Response

    pathologic complete response was defined as no residual invasive cancer in the breast and the axillary lymph nodes.

    Measured: 12 weeks or 24 weeks depending on arm assignment

  3. Clinical Response

    Measured: 12 weeks or 24 weeks depending on arm assignment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2009 (estimated)
  2. Study startOct 2011
  3. Primary completionNov 2014
  4. Study completionJan 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00999804
Sponsor's protocol ID
H-25846
Acronym
HELEX
Status last verified
Feb 2025
First submitted
21 Oct 2009
Last updated
12 Mar 2025
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 31662331

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib, Letrozole and Trastuzumab in people with Breast Cancer, run by Baylor Breast Care Center at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (time frame: 12 or 24 week depending the arm assignment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00999804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025.

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