Akt Inhibitor MK2206 in Combination With Lapatinib Ditosylate in Patients With Advanced or Metastatic Solid Tumors or Breast Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: A Phase I Study of MK-2206 in Combination With Lapatinib in Refractory Solid Tumors Followed by Dose-Expansion in Advanced HER2+ Breast Cancer

Status Completed

Clinical Trial Summary

This phase I trial studies the side effects and the best dose of Akt inhibitor MK2206 and lapatinib ditosylate in treating patients with solid tumors or breast cancer that has spread to other places in the body. Akt inhibitor MK2206 and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of MK-2206 (Akt inhibitor MK2206) in combination with lapatinib (lapatinib ditosylate) in adult subjects with advanced solid tumors. (Dose Escalation Cohort) II. To further evaluate the safety of MK-2206 in combination with lapatinib administered to patients with locally advanced and unresectable or metastatic human epidermal growth factor receptor 2 positive (HER2+) breast cancer, previously treated with trastuzumab. (Dose Expansion Cohort)

SECONDARY OBJECTIVES:

I. To determine the clinical activity of MK-2206 in combination with lapatinib administered to subjects with advanced solid tumors. (Dose Escalation Cohort) II. To describe the dose-limiting toxicities (DLTs) of combined MK-2206 and lapatinib. (Dose Escalation Cohort) III. To determine the safety of MK-2206 and lapatinib administered in combination. (Dose Escalation Cohort) IV. To determine the pharmacokinetic and pharmacogenomic profile of MK-2206 in combination with lapatinib. (Dose Escalation Cohort) V. To assess for target (HER2-phosphoinositide 3-kinase [PI3K]-protein kinase B [AKT] pathway) inhibition via peripheral blood mononuclear cells (PBMCs) in the dose escalation cohort. (Dose Escalation Cohort) VI. To determine the clinical activity of MK-2206 and lapatinib administered in combination to patients with locally advanced and unresectable or metastatic HER2+ breast cancer. (Dose Expansion Cohort) VII. To determine the progression-free rate following MK-2206 in combination with lapatinib when administered at the MTD level to subjects with HER2+ metastatic breast cancer (MBC). (Dose Expansion Cohort) VIII. To determine the pharmacokinetic and pharmacogenomic profiles of MK-2206 in combination with lapatinib. (Dose Expansion Cohort) IX. To assess for mechanisms of lapatinib resistance by evaluating tumor tissue for phosphatase and tensin homolog (PTEN) loss using immunohistochemistry. (Dose Expansion Cohort) X. To assess for mechanisms of lapatinib resistance by evaluating tumor tissue for oncogenic mutations in PI3K. Tumor response to combination therapy with lapatinib and MK-2206 will be correlated with presence/absence of PI3K activating mutations and PTEN loss. (Dose Expansion Cohort) XI. To assess for mechanisms of lapatinib resistance by assessing for target (HER2-PI3K-AKT pathway) inhibition via peripheral blood mononuclear cells (PBMCs). (Dose Expansion Cohort)

OUTLINE: This is a dose-escalation study.

Patients receive Akt inhibitor MK2206 orally (PO) every other day (QOD) for 28 days (35 days for course 1) and lapatinib ditosylate PO once daily (QD) or twice daily (BID) on days 1-28 (days 9-35 for course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and patients on the expanded cohort are followed up every 3 months. ;

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• HER2-positive Breast Cancer
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer
• Stage IV Breast Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT01245205
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: November 2010