Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer
|ClinicalTrials.gov Identifier: NCT01480154|
Recruitment Status : Active, not recruiting
First Posted : November 28, 2011
Last Update Posted : May 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Hormone-Resistant Prostate Carcinoma Recurrent Melanoma Recurrent Prostate Carcinoma Recurrent Renal Cell Carcinoma Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Stage IV Prostate Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7||Drug: Akt Inhibitor MK2206 Drug: Hydroxychloroquine Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. To define the maximum tolerated dose (MTD) of MK-2206 (Akt inhibitor MK2206) and hydroxychloroquine (HCQ) when used in combination.
I. To determine side effects and activity of MK-2206 and hydroxychloroquine when used in combination.
II. To determine if hydroxychloroquine alters the pharmacokinetics of MK-2206 due to a drug-drug interaction.
III. To validate biomarkers for autophagy detection.
OUTLINE: This is a dose-escalation study of Akt inhibitor MK-2206.
Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, and 15. Beginning on course 2, patients also receive hydroxychloroquine PO twice daily (BID) on days 1-21. 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)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of MK-2206 and Hydroxychloroquine in Solid Tumors, Melanoma, Renal and Prostate Cancer to Examine the Role of Autophagy in Tumorigenesis|
|Actual Study Start Date :||November 23, 2011|
|Estimated Primary Completion Date :||December 1, 2018|
Experimental: Treatment (Akt inhibitor MK2206, hydroxychloroquine)
Patients receive Akt inhibitor MK2206 PO on days 1, 8, and 15. Beginning on course 2, patients also receive hydroxychloroquine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt Inhibitor MK2206
Other Name: MK2206
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- MTD of Akt inhibitor MK-2206 as assessed by CTCAE version 4.0 [ Time Frame: 21 days ]
- Dose-limiting toxicity rate as assessed by CTCAE version 4.0 [ Time Frame: 21 days ]
- Changes in expression pattern of markers Beclin1, LC3, and p62 by immunohistochemistry (IHC), Western blotting, and number of autophagosomes by electron microscope (EM) [ Time Frame: Baseline to 4 weeks ]Spaghetti plots or boxplots at time points will be produced for each marker and for EM. Appropriate transformations of the measurements will be carried out to normalize the data. Descriptive summary statistics will be provided for each type of measure at each time point.
- Change in autophagy activity induced by hydroxychloroquine as measured by the amount of autophagosomes by EM [ Time Frame: Baseline to 4 weeks ]Student t-test and Wilcoxon nonparametric tests will be conducted.
- Validation of Beclin1, LC3, and p62 as markers for autophagy measured by EM [ Time Frame: Up to 4 weeks ]Linear mixed models will be fitted to the data, EM as the independent variable, the 3 markers and time points as fixed effects, plus a subject-specific random effect. A backward variable selection will be carried out for the 3 markers until a final model is selected. An ROC curve will be produced. The log-transformed ratio of LC3-II/LC3-I and difference in the log-transformed ratios of LC3-II./LC3-I pre-post treatment between high autophagy activity (HA, >= 6 AV/cell) and low autophagy activity (LA, < 6 AV/cell) will be analyzed for evaluating treatment effect using a two sided paired t-test.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01480154
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Mark Stein||Rutgers Cancer Institute of New Jersey|