MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia
This phase I trial is studying the side effects, best way to give, and best dose of Akt inhibitor MK2206 (MK2206) in treating patients with recurrent or refractory solid tumors or leukemia. MK2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Accelerated Phase Chronic Myelogenous Leukemia
Acute Leukemias of Ambiguous Lineage
Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
Acute Undifferentiated Leukemia
Aggressive NK-cell Leukemia
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Blastic Phase Chronic Myelogenous Leukemia
Blastic Plasmacytoid Dendritic Cell Neoplasm
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Juvenile Myelomonocytic Leukemia
Mast Cell Leukemia
Myeloid/NK-cell Acute Leukemia
Noncutaneous Extranodal Lymphoma
Post-transplant Lymphoproliferative Disorder
Primary Central Nervous System Hodgkin Lymphoma
Primary Central Nervous System Non-Hodgkin Lymphoma
Progressive Hairy Cell Leukemia, Initial Treatment
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: Akt inhibitor MK2206
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:||A Phase I Study of MK-2206, an AKT Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia|
- MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to incidence of dose-limiting toxicities (DLTs) graded using CTCAE v4.0 (Part A) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The MTD will be the maximum dose at which fewer than one-third of patients experience DLT during course 1 of therapy.
- Pharmacokinetic (PK) parameters of Akt inhibitor MK-2206 [ Time Frame: Baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose and 6-8 hours post-dose (optional) day 15 (Schedule 1); baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose days 8 and 15; 6-8 hours post-dose day 15 (optional) (Schedule 2) ] [ Designated as safety issue: No ]Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
- Levels of activation of downstream signaling molecules [ Time Frame: Up to day 15 of course 1 ] [ Designated as safety issue: No ]Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.
- Mutations or amplification of upstream signaling molecules [ Time Frame: Baseline ] [ Designated as safety issue: No ]Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.
|Study Start Date:||January 2011|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor)
Patients receive oral Akt inhibitor MK2206 every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Other Name: MK2206Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
l. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of MK-2206 (Akt inhibitor MK2206) administered orally every other day (schedule 1) or once weekly (schedule 2) to children with refractory or recurrent solid malignancies, including central nervous system (CNS) tumors or lymphomas.
II. To define and describe the toxicities of MK-2206 in children with refractory solid malignancies administered on this schedule.
III. To assess the tolerability of MK-2206 at the solid tumor MTD in patients with recurrent or refractory leukemia.
IV. To characterize the pharmacokinetics of MK-2206 in children with recurrent or refractory cancer. (exploratory)
I. To preliminarily define the antitumor activity of MK-2206 within the confines of a phase 1 study.(exploratory) II. To evaluate biological activity of MK-2206 by measuring phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling in tumor and peripheral blood mononuclear cells and measure the expression of biomarkers related to AKT activation phenotypes. (exploratory)
OUTLINE: This is a dose-escalation study (part A) followed by treatment at the maximum-tolerated dose (part B).
Patients receive Akt inhibitor MK2206 orally (PO) every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01231919
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|Principal Investigator:||Maryam Fouladi||COG Phase I Consortium|