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
Adenocarcinoma of the Gastroesophageal Junction
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
Drug: Akt inhibitor MK2206
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of MK-2206 in Combination With Trastuzumab and Lapatinib in HER2-Positive Breast and Gastric Cancer|
- MTD of Akt inhibitor MK-2206 and lapatinib ditosylate in combination with trastuzumab determined by dose limiting toxicities as measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4 [ Time Frame: 21 days ]Described by frequency and grade, by course and over all courses, with the maximum grade over all courses used as the summary measure per patient.
- Median progression free survival (PFS) [ Time Frame: Up to 3 years ]Estimated using Kaplan-Meier estimates along with 95% confidence intervals.
- Median and range of duration of response [ Time Frame: Up to 3 years ]Estimated using Kaplan-Meier estimates along with 95% confidence intervals.
- Overall response rate (ORR), evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: 21 days ]Calculated and presented with 95% confidence intervals. Kaplan-Meier methods or the Chi-square test will be used to assess whether PI3K-PTEN mutation status of metastatic tissue is correlated with PFS or ORR. In addition, comparisons of the HER-2 status and PI3K-PTEN mutation status of the primary tumor will be compared with that from metastatic tissue using paired tests, such as the Mc Nemar's Chi-square test.
|Study Start Date:||September 2012|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (MK2206, lapatinib ditosylate, trastuzumab)
Patients receive Akt inhibitor MK2206 PO on days 1, 8, and 15; lapatinib ditosylate PO QD on days 1-21 or on days 1-3, 8-10, and 15-17; and trastuzumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Other Name: MK2206Biological: trastuzumab
Other Names:Drug: lapatinib ditosylate
Other Names:Other: laboratory biomarker analysis
Optional correlative studies
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01705340
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Devika Gajria||Memorial Sloan Kettering Cancer Center|