MK2206 and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Metastatic Breast Cancer
This phase I clinical trial is studying the side effects and best dose of MK2206 when given with paclitaxel and to see how well they work in treating patients with locally advanced or metastatic solid tumors or metastatic breast cancer. MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving MK2206 with chemotherapy may kill more cancer cells.
Recurrent Breast Cancer
Stage IV Breast Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Akt inhibitor MK2206
Other: circulating tumor cell analysis
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase Ib Dose Escalation and Biomarker Study of MK-2206 in Combination With Standard Doses of Weekly Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors With an Expansion in Advanced Breast Cancer|
- MTD of the combination of MK-2206 and weekly paclitaxel determined by dose-limiting toxicities (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- Determination of the antitumor activity of the combination in metastatic breast cancer (Expansion phase) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||January 2011|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 PO QD on days 2, 9, and 16. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Other Name: MK2206Drug: paclitaxel
Other Names:Other: circulating tumor cell analysis
Other Name: CTC analysisOther: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
I. To determine the MTD of the combination of MK-2206 and weekly paclitaxel. (Dose-escalation phase) II. To determine the safety and anti-tumor activity of the combination in metastatic breast cancer. (Expansion phase)
I. To determine the pharmacokinetics of MK-2206 and weekly paclitaxel used in combination.
II. To determine the safety of MK-2206 and weekly paclitaxel used in combination.
III. To evaluate the toxicities and tolerability of the combination. IV. To document anti-tumor activity. V. To determine baseline molecular markers that may predict clinical activity. VI. To determine pharmacodynamic markers in blood and tumor tissue that may predict an increase in apoptosis (by cleaved caspase 3) and clinical activity.
VII. To determine concordance of PIK3CA and PTEN status between primary tumor and distant metastasis.
VIII. To determine concordance of PIK3CA status of circulating tumor cells and distant metastasis.
OUTLINE: This is a multicenter, dose-escalation study of Akt inhibitor MK2206.
Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 orally (PO) once daily (QD) on days 2, 9, and 16. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue and blood samples are collected periodically for pharmacodynamic and pharmacokinetic studies.
After completion of study treatment, patients are followed up for 3 weeks.
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Ana Maria Gonzalez-Angulo||M.D. Anderson Cancer Center|