MK2206 and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01263145|
Recruitment Status : Completed
First Posted : December 20, 2010
Last Update Posted : August 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Recurrent Breast Carcinoma Stage IV Breast Cancer||Drug: Akt Inhibitor MK2206 Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Pharmacological Study||Phase 1|
I. To determine the maximum tolerated dose (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 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and phosphatase and tensin homolog (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 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.
After completion of study treatment, patients are followed up for 3 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 5, 2011|
|Actual Primary Completion Date :||October 19, 2012|
|Actual Study Completion Date :||October 19, 2012|
Experimental: Treatment (Akt inhibitor MK2206 and paclitaxel)
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
Given POOther: Laboratory Biomarker Analysis
Correlative studiesDrug: Paclitaxel
Given IVOther: Pharmacological Study
- Antitumor activity of the combination in metastatic breast cancer (Expansion phase) [ Time Frame: Up to 3 weeks after completion of study treatment ]
- MTD of the combination of MK-2206 and paclitaxel defined as the dose level in which less than or equal to 1 out of 6 patients develop dose limiting toxicity assessed using Common Terminology Criteria for Adverse Events version 4 (Phase I) [ Time Frame: 21 days ]
- Change in average number of circulating tumor cells (CTCs) [ Time Frame: Baseline to up to 2 weeks ]Will be determined by chi-square analysis or Fisher's Exact test and compared by Student t-test.
- Change in multiplex proteomics [ Time Frame: Baseline to up to day 17 ]
- Change in percentage of biomarkers assessed using immunohistochemistry [ Time Frame: Baseline to up to 2 weeks ]
- Change in percentage of marker of proliferation Ki-67 (Ki-67) positive cells [ Time Frame: Baseline to up to 2 weeks ]Will be calculated using a two-sided one-sample t-test, at a significance level of 0.05.
- Change in reverse phase proteomic arrays (RPPA) [ Time Frame: Baseline to up to day 8 ]Will be analyzed using the Wilcoxon rank test.
- Pharmacokinetic parameters of Akt inhibitor MK2206 [ Time Frame: On days 1-3, 5, 8, 16, 17, and 19 of course 1 and then on day 1 of all subsequent courses ]Standard analyses for the pharmacokinetic endpoints will be conducted, including summary of descriptive measures, e.g., tabulation of frequencies for categorical variables, numerical (mean, range, standard deviation, 95% confidence intervals) and graphical (box plots, histograms) summary of the distribution for continuous endpoints, correlation analyses (Pearson and Spearman), and linear and nonlinear regression analyses, etc.
- Pharmacokinetic parameters of paclitaxel [ Time Frame: On days 1, 2, 15, and 16 of course 1 ]Standard analyses for the pharmacokinetic endpoints will be conducted, including summary of descriptive measures, e.g., tabulation of frequencies for categorical variables, numerical (mean, range, standard deviation, 95% confidence intervals) and graphical (box plots, histograms) summary of the distribution for continuous endpoints, correlation analyses (Pearson and Spearman), and linear and nonlinear regression analyses, etc.
- Change in expression of plasma markers [ Time Frame: Baseline to up to day 17 ]The marker expression will be compared by Student t-test.
- PIK3CA mutation status [ Time Frame: Up to day 17 ]Chi-square or Fisher's exact status will be used to calculate associations between PIK3CA status and clinical parameters.
- Prevalence of single nucleotide polymorphisms (SNPs) in PI3K pathway genes [ Time Frame: Up to day 17 ]Descriptive analysis will be performed.
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): NCT01263145
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Funda Meric-Bernstam||M.D. Anderson Cancer Center|