NCT01281163

Lapatinib Ditosylate and Akt Inhibitor MK2206 in Treating Women With Metastatic Breast Cancer

A Phase 1b Dose-Escalation Study of the AKT Inhibitor MK-2206 (NSC# 749607) Plus Lapatinib (NSC# 727989) Administered in Patients With HER2 Positive Metastatic Breast Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of lapatinib ditosylate and Akt inhibitor MK2206 in treating women with metastatic breast cancer. Lapatinib ditosylate and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of continuous daily administration of lapatinib (lapatinib ditosylate) in combination with weekly administration of MK2206 (AKT inhibitor MK2206) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. II. To determine the dose-limiting toxicity (DLT) and identify the maximum-tolerated dose (MTD) and/or recommended phase II dose (RP2D) for this administration schedule. SECONDARY OBJECTIVES: I. To determine the pharmacokinetics (PK) of MK2206 and lapatinib, each given alone and in the combination. II. To evaluate potential pharmacogenetic influence of the candidate drug metabolizing enzymes and transporters on the PK of MK2206 and lapatinib. III. To evaluate the change in select breast cancer biomarkers in the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathways, (e.g., phosphorylated \[p\]PTEN, PTEN, pAkt, Akt, phosphorylated glycogen synthase kinase (pGSK)3-beta, GSK3-beta), Wnt/beta-catenin pathway (e.g., activated beta-catenin (ABC), beta-catenin), and pHER2. IV. To evaluate the change in breast cancer stem cell (BCSC) biomarkers, aldehyde dehydrogenase (ALDH)1 and cluster of differentiation (CD) 44+/CD24-, before and after 2 weeks of treatment with the combination of MK2206 and lapatinib at the MTD. The percent change in BCSCs in tumor biopsies will also be evaluated. V. To determine tumor response in patients with measurable disease as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), and by percent change in BCSCs within the tumor before vs after 2 weeks of combination treatment. VI. To perform genomic profiling of the tumor cell and BCSC populations before and after 2 weeks of treatment with the combination of MK2206 and lapatinib at the MTD. OUTLINE: This is a phase I, dose-escalation study followed by an expansion cohort study. Patients receive lapatinib ditosylate orally (PO) once daily (QD) on days 1 and 15-28 of course 1 and on days 1-28 of subsequent courses. Patients also receive AKT inhibitor MK2206 PO QD on days 8, 15, and 22 of course 1 and on days 1, 8, 15, and 22 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 30 days.

Conditions

• Estrogen Receptor Negative
• Estrogen Receptor Positive
• HER2/Neu Positive
• Progesterone Receptor Negative
• Progesterone Receptor Positive
• Recurrent Breast Carcinoma
• Stage IV Breast Cancer

Interventions

Type	Name	Description
DRUG	Akt Inhibitor MK2206	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Lapatinib Ditosylate	Given PO
OTHER	Pharmacogenomic Study	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2011-01-01
• Primary completion: 2013-12-01
• Completion: 2013-12-01
• First posted: 2011-01-21
• Last updated: 2015-08-27

Locations

5 sites across 1 country: United States