Lapatinib + Trastuzumab for Breast Cancer

(HELEX Trial)

Not currently recruiting at 7 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new breast cancer treatment using a combination of drugs: lapatinib (Tykerb) and trastuzumab (Herceptin), with letrozole (Femara) added for some participants. The goal is to determine if this combination can effectively target and treat breast cancers that overexpress HER2, a protein that can promote tumor growth. The trial seeks women with locally advanced, HER2-positive breast cancer, meaning their cancer has high levels of this specific protein. Participants will be divided into two groups, one receiving a 24-week treatment and the other a 12-week treatment. Women with other serious health conditions or previous breast cancer treatments in the last five years are not eligible. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using lapatinib and trastuzumab together has been safe in past studies. For example, one study found that patients who took both drugs responded well, achieving good control over their cancer. Most participants did not experience severe side effects, indicating the combination was generally well-tolerated.

Another study demonstrated that these drugs effectively controlled the disease. Most patients could continue the treatment, suggesting it was manageable for them.

Both lapatinib and trastuzumab are already used to treat breast cancer, providing extensive safety information. This makes using both drugs together a well-researched option with a strong safety record. However, like any treatment, side effects can occur, so discussing these with a doctor is important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lapatinib and Trastuzumab for breast cancer because it targets cancer cells in two powerful ways. Unlike some treatments that focus on either HER2 or hormone receptors, this combo addresses both, potentially making it effective for a broader range of patients. Lapatinib blocks signals that encourage cancer cell growth, while Trastuzumab attaches to the HER2 protein on cancer cells, marking them for destruction. For patients with hormone receptor-positive cancers, adding Letrozole helps by further disrupting cancer growth fueled by hormones. This multi-pronged approach could lead to better outcomes compared to current treatments that often target just one pathway.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that combining lapatinib and trastuzumab can be effective for certain breast cancers, particularly HER2-positive breast cancer, where cancer cells have high levels of the HER2 protein. One study found that using both drugs together resulted in no detectable cancer cells in about 47% of cases, outperforming the use of either drug alone. In studies with mice, this combination also reduced tumor growth and sometimes caused tumors to disappear completely. In this trial, participants will receive either a 24-week or a 12-week regimen of lapatinib plus trastuzumab. Those who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Overall, evidence suggests that using lapatinib and trastuzumab together targets cancer cells more effectively than using them separately.24678

Who Is on the Research Team?

MR

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

You are in good enough health and expected to live for at least 6 more months.
You have not had any other cancers, except for certain types of skin and cervical cancers that were treated and are not a current concern.
Signed informed consent
See 5 more

Exclusion Criteria

You have a serious, long-term health condition.
Inability or unwillingness to comply with, or follow study procedures
Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lapatinib plus trastuzumab for either 12 weeks or 24 weeks, with endocrine therapy for ER/PR positive patients

12 or 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

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
Trial Overview The study examines the effectiveness of combining Trastuzumab (Herceptin), Lapatinib, and possibly Letrozole as treatments for breast cancer that overexpresses HER2. It aims to overcome resistance to therapy by targeting different molecular mechanisms within the tumor cells.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: 24-week armExperimental Treatment3 Interventions
Group II: 12-week armActive Control3 Interventions

Lapatinib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Tykerb for:
🇪🇺
Approved in European Union as Tyverb for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor Breast Care Center

Lead Sponsor

Trials
16
Recruited
750+

Translational Breast Cancer Research Consortium

Collaborator

Trials
27
Recruited
3,100+

GlaxoSmithKline

Industry Sponsor

Trials
4,834
Recruited
8,389,000+
Headquarters
London, UK
Known For
Vaccines & Medicines
Top Products
**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)
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Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron profile image

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase III trial, lapatinib combined with letrozole significantly improved progression-free survival (PFS) in postmenopausal women with HER2-negative, low estrogen receptor (ER) expression metastatic breast cancer, showing a median PFS of 13.6 months compared to 6.7 months with letrozole alone.
No benefit from lapatinib was observed in patients with higher ER expression, indicating that low ER levels may be a key factor in determining which patients benefit from this treatment combination.
Quantitative ER and PgR assessment as predictors of benefit from lapatinib in postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.Finn, RS., Press, MF., Dering, J., et al.[2018]
HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.
Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.
Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer.Stanowicka-Grada, M., Senkus, E.[2023]
In a study of 23 patients with HER2-positive metastatic breast cancer, the combination of Lapatinib and Trastuzumab resulted in a median progression-free survival of 7 months, indicating effective treatment outcomes.
The treatment was generally well-tolerated, although 7 patients experienced adverse events, and 4 had to stop treatment due to toxicity, highlighting the importance of monitoring for side effects.
[Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer: experience of use].García-Muñoz, C., Cortijo-Cascajares, S., Cañamares-Orbis, I., et al.[2018]

Citations

Is the Improved Efficacy of Trastuzumab and Lapatinib ...Overall, the TBCRC 006 trial demonstrated that the combination of trastuzumab and lapatinib with anti-estrogen therapy can be effective in HR+ HER2+ breast ...
Trastuzumab plus lapatinib or chemotherapy in patients with ...Conclusions. While efficacy differences were not significant, trastuzumab with lapatinib showed better QoL despite higher adverse event rates, ...
Lapatinib and lapatinib plus trastuzumab therapy versus ...The CHER-Lob and TRIO-US B07 proved that trastuzumab plus lapatinib treatment has a better pathologic complete response (pCR) outcome [21, 22].
Clinical outcomes of patients with breast cancer relapsing ...Out of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the ...
SABCS Coverage: Trastuzumab Superior to Lapatinib in ...Assessing pCR as the absence of cancer cells in the breast and lymph nodes produced a rate of 46.9% in the combination arm, compared with 27.6% in the ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/25130998/
Lapatinib with trastuzumab for HER2-positive early breast ...Median survival follow-up was 3·84 years (IQR 3·60-4·24), and 3-year overall survival was 93% (95% CI 87-96) for lapatinib, 90% (84-94) for trastuzumab, and 95% ...
NCT00429299 | Neoadjuvant Study With Chemotherapy ...Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with chemotherapy in the preoperative (neoadjuvant) treatment of early breast ...
Her2 positive metastatic breast cancer treated with low ...The disease control rate with lapatinib was 61.7%. The median progression-free survival was 7 months (95% CI: 5.6–8.4 months). The median ...
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