Lapatinib + Trastuzumab for Breast Cancer
(HELEX Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot take any investigational drugs or lapatinib prohibited medications while participating.
Is the combination of Lapatinib and Trastuzumab safe for treating breast cancer?
The combination of Lapatinib and Trastuzumab has been studied for safety in breast cancer treatment. Common side effects of Lapatinib include diarrhea and rash, which are usually mild or moderate. Serious heart-related side effects are rare, and the treatment is generally well tolerated in patients.12345
What makes the drug combination of Lapatinib, Letrozole, and Trastuzumab unique for treating breast cancer?
This drug combination is unique because it targets HER2-positive breast cancer by using both Lapatinib and Trastuzumab, which are HER2-receptor inhibitors, and Letrozole, which is a hormone therapy. This approach is particularly beneficial for patients whose cancer has progressed despite previous treatments with other HER2-targeted therapies.26789
What data supports the effectiveness of the drug combination Lapatinib and Trastuzumab for breast cancer?
Research shows that combining Lapatinib and Trastuzumab is effective for treating HER2-positive metastatic breast cancer, especially in patients who have been previously treated with these drugs. This combination has been shown to improve outcomes and prolong survival in patients with this type of breast cancer.2681011
Who Is on the Research Team?
Mothaffar Rimawi, MD
Principal Investigator
Baylor College of Medicine
Are You a Good Fit for This Trial?
This trial is for women over 18 with advanced breast cancer larger than 2 cm, HER2 positive, and no Stage IV disease. They must have a life expectancy over 6 months, good performance status, normal organ function tests, and no other cancers or severe illnesses in the last five years. Participants cannot be pregnant and must agree to use contraception.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive lapatinib plus trastuzumab for either 12 weeks or 24 weeks, with endocrine therapy for ER/PR positive patients
Follow-up
Participants are monitored for safety and effectiveness after treatment
Extension
Participants may continue to receive lapatinib plus trastuzumab in an extended regimen to assess long-term safety and tolerability
What Are the Treatments Tested in This Trial?
Interventions
- Lapatinib
- Letrozole
- Trastuzumab
Lapatinib is already approved in United States, European Union for the following indications:
- Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab
- Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor Breast Care Center
Lead Sponsor
Translational Breast Cancer Research Consortium
Collaborator
GlaxoSmithKline
Industry Sponsor
Dame Emma Walmsley
GlaxoSmithKline
Chief Executive Officer since 2017
MA in Classics and Modern Languages from Oxford University
Dr. Hal Barron
GlaxoSmithKline
Chief Medical Officer since 2018
MD from Harvard Medical School