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
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|ClinicalTrials.gov Identifier: NCT01705340|
Recruitment Status : Terminated
First Posted : October 12, 2012
Last Update Posted : September 30, 2013
|Condition or disease||Intervention/treatment||Phase|
|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 Biological: trastuzumab Drug: lapatinib ditosylate Other: laboratory biomarker analysis||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of MK-2206 in Combination With Trastuzumab and Lapatinib in HER2-Positive Breast and Gastric Cancer|
|Study Start Date :||September 2012|
|Actual Primary Completion Date :||May 2013|
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: MK2206
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Optional correlative studies
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|