Lapatinib + Trastuzumab for Breast Cancer
(HELEX Trial)

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen ByMothaffar Rimawi, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Baylor Breast Care Center

No Placebo Group

Prior Safety Data

Trial Summary

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.

Eligibility Criteria

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.

All patients must be female and at least 18 years of age

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.

+6 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

+9 more

Participant Groups

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.

2Treatment groups

Experimental Treatment

Active Control

Group I: 24-week armExperimental Treatment3 Interventions

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.

Group II: 12-week armActive Control3 Interventions

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

🇺🇸 Approved in United States as Tykerb for:

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

🇪🇺 Approved in European Union as Tyverb for:

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