MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia
A Phase I Study of MK-2206, an AKT Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia
5 other identifiers
interventional
45
2 countries
25
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 29, 2010
CompletedFirst Posted
Study publicly available on registry
November 1, 2010
CompletedStudy Start
First participant enrolled
January 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2013
CompletedApril 29, 2014
April 1, 2013
2.2 years
October 29, 2010
April 28, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
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)
The MTD will be the maximum dose at which fewer than one-third of patients experience DLT during course 1 of therapy.
28 days
Secondary Outcomes (4)
Pharmacokinetic (PK) parameters of Akt inhibitor MK-2206
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)
Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1
Up to 30 days
Levels of activation of downstream signaling molecules
Up to day 15 of course 1
Mutations or amplification of upstream signaling molecules
Baseline
Study Arms (1)
Treatment (Akt inhibitor)
EXPERIMENTALPatients 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.
Interventions
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have a body surface area \> 0.5 m\^2 when enrolling on dose levels 0 or 1 of the every other day schedule; no body surface area (BSA) restrictions apply to patients enrolling on higher dose levels; no BSA restrictions apply to patients enrolling on any dose level of the weekly schedule.
- Diagnosis:
- Part A (both schedules): Patients must have a diagnosis of recurrent or refractory solid tumors, including central nervous system (CNS) tumors or lymphoma; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Part B (both schedules): Patients must have a diagnosis of recurrent or refractory leukemia
- Disease status:
- Solid tumors: Patients must have either measurable or evaluable disease
- Leukemia: Patients must have \>= 5% blasts in the bone marrow; active extramedullary disease (except for leptomeningeal disease) may also be present
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; note: neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
- Myelosuppressive chemotherapy:
- Solid tumors: Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
- Leukemia:
- Patients with leukemia who relapse while receiving standard maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study
- Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy. At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
- +35 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anticancer agents are not eligible \[except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy\]; patients with leukemia may receive intrathecal therapy
- Patients must not be receiving enzyme-inducing anticonvulsants
- Patients receiving insulin or growth hormone therapy are not eligible
- Patients on medications that may cause corrected QT (QTc) interval prolongation are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
- Patients must be able to swallow whole tablets; nasogastric or G tube administration is not allowed
- Patients who have an uncontrolled infection are not eligible
- Patients with known type I or type II diabetes mellitus are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Childrens Hospital of Orange County
Orange, California, 92868-3874, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Mark O Hatfield-Warren Grant Magnuson Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maryam Fouladi
COG Phase I Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 29, 2010
First Posted
November 1, 2010
Study Start
January 1, 2011
Primary Completion
April 1, 2013
Last Updated
April 29, 2014
Record last verified: 2013-04