Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy

Conditions

• Breast Cancer

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lapatinib — DRUG
  1000 mg of Lapatinib by mouth daily
• Letrozole — DRUG
  Letrozole, 2.5 mg by mouth daily (for hormone receptor positive participants only)
• Trastuzumab — DRUG
  6 mg/kg intravenously, every 3 weeks

Study Details

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.

Key Dates

Start date

Oct 31, 2011

Status verified

Feb 2025

Primary completion

Nov 30, 2014

Completion

Jan 31, 2026

Study Design

Enrollment

128 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: 24-week arm
  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.
• Active Comparator: 12-week arm
  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.

Primary Outcome Measure

Pathologic Complete Response [ Time Frame: 12 or 24 week depending the arm assignment ]

Locations (8)

Find similar trials in Birmingham, AL

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