Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors or Prostate or Kidney Cancer
This phase I trial studies the side effects and the best dose of Akt inhibitor MK2206 together with hydroxychloroquine in treating patients with advanced solid tumors or prostate or kidney cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving Akt inhibitor MK2206 together with hydroxychloroquine may kill more tumor cells.
Recurrent Prostate Cancer
Recurrent Renal Cell Cancer
Stage III Prostate Cancer
Stage III Renal Cell Cancer
Stage IV Prostate Cancer
Stage IV Renal Cell Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Akt inhibitor MK2206
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- MTD of Akt inhibitor MK-2206 as assessed by CTCAE version 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Dose-limiting toxicity (DLT) rate as assessed by CTCAE version 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- 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: From baseline to 4 weeks ] [ Designated as safety issue: No ]Descriptive summary statistics will be provided for each type of measure at each time point.
- Change in autophagy activity induced by hydroxychloroquine [ Time Frame: From baseline to 4 weeks ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]A backward variable selection will be carried out for the 3 markers until a final model is selected. An ROC curve will be produced.
|Study Start Date:||November 2011|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (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: MK2206Drug: hydroxychloroquine
Other Name: HCQOther: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To define the maximum-tolerated dose (MTD) of Akt inhibitor MK2206 (MK-2206) 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.
Patients undergo peripheral blood mononuclear cells collections and bone marrow biopsies at baseline and during study for pharmacokinetics and biomarker studies.
After completion of study treatment, patients are followed up for 4 weeks.
|United States, New Jersey|
|Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Mark N. Stein 732-235-7464 firstname.lastname@example.org|
|Principal Investigator: Mark N. Stein|
|Principal Investigator:||Mark Stein||Cancer Institute of New Jersey|