Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

HER2-positive Breast Cancer Clinical Trial

Official title: A Phase I Study of MK-2206 in Combination With Trastuzumab and Lapatinib in HER2-Positive Breast and Gastric Cancer

Status Terminated

Clinical Trial Summary

This phase I trial studies the side effects and best dose of Akt inhibitor MK2206 and lapatinib ditosylate when given together with trastuzumab in treating patients with locally advanced or metastatic human epidermal growth factor receptor-2 (HER2)-positive breast, gastric, or gastroesophageal cancer that cannot be removed by surgery. Akt inhibitor MK2206 and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving Akt inhibitor MK2206 and lapatinib ditosylate together with trastuzumab may kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To define maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of MK-2206 (Akt inhibitor MK2206) in combination with trastuzumab and lapatinib (lapatinib ditosylate) in adult patients with locally advanced or metastatic HER2-positive breast or gastric cancer; two schedules of lapatinib administration will be examined-continuous daily dosing and pulsatile dosing.

SECONDARY OBJECTIVES:

I. To provide preliminary assessment of the safety and tolerability of MK-2206 administered in combination with epidermal growth factor receptor (EGFR)/HER2 blockade via trastuzumab and lapatinib in adult patients with a locally advanced or metastatic HER2-positive breast or gastric tumor.

II. To explore the anti-tumor activity of MK-2206 in combination with trastuzumab and lapatinib in patients with advanced HER2-positive solid tumor.

TERTIARY OBJECTIVES:

I. To correlate the anti-tumor activity of MK-2206 in combination with trastuzumab and lapatinib in HER2-positive solid tumor patients with phosphoinositide 3-kinase (PI3K) pathway activation events, e.g., phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) or phosphatase and tensin homolog (PTEN) and other related gene mutations and expressions; to compare the HER2 and PI3K-PTEN mutation status of the primary tumor to metastatic tumor biopsy when available.

OUTLINE: This is a dose-escalation study of Akt inhibitor MK2206 and lapatinib ditosylate.

Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, and 15; lapatinib ditosylate PO once daily (QD) on days 1-21 or on days 1-3, 8-10, and 15-17; and trastuzumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Breast Neoplasms
• Breast Neoplasms, Male
• Esophageal Neoplasms
• HER2-positive Breast Cancer
• Male Breast Cancer
• Recurrent Breast Cancer
• Recurrent Esophageal Cancer
• Recurrent Gastric Cancer
• Stage IIIC Breast Cancer
• Stage IIIC Esophageal Cancer
• Stage IIIC Gastric Cancer
• Stage IV Breast Cancer
• Stage IV Esophageal Cancer
• Stage IV Gastric Cancer
• Stomach Neoplasms

• NCT number: NCT01705340
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1
• Start date: September 2012