MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01231919
First received: October 29, 2010
Last updated: September 27, 2013
Last verified: September 2013

October 29, 2010
September 27, 2013
January 2011
April 2013   (final data collection date for primary outcome measure)
MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to dose-limiting toxicities (DLTs) graded using CTCAE v4.0 [ 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.
  • Maximum-tolerated dose (MTD) and/or recommended phase 2 dose of Akt inhibitor MK2206 [ Designated as safety issue: Yes ]
  • Toxicities of this treatment in children with refractory solid malignancies administered on this schedule [ Designated as safety issue: Yes ]
  • Tolerability of this treatment at the solid tumor MTD in patients with recurrent or refractory leukemia [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01231919 on ClinicalTrials.gov Archive Site
Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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

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.

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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 PI3K/AKT/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 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.

After completion of study treatment, patients are followed up for 30 days.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Undifferentiated Leukemia
  • Angioimmunoblastic T-cell Lymphoma
  • 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
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Mast Cell Leukemia
  • Nodal Marginal Zone B-cell Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Primary Central Nervous System Hodgkin Lymphoma
  • Primary Central Nervous System Non-Hodgkin Lymphoma
  • Progressive Hairy Cell Leukemia, Initial Treatment
  • Prolymphocytic Leukemia
  • 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 Cutaneous T-cell Non-Hodgkin 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
  • T-cell Large Granular Lymphocyte Leukemia
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Waldenström Macroglobulinemia
  • Drug: Akt inhibitor MK2206
    Given PO
    Other Name: MK2206
  • Other: diagnostic laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
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.
Interventions:
  • Drug: Akt inhibitor MK2206
  • Other: diagnostic laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
96
Not Provided
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis meets one of the following criteria:

    • Part A (both schedules):

      • Patients must have a diagnosis of recurrent or refractory solid tumors, including 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
  • Patients with solid tumors must have either measurable or evaluable disease
  • Patients with leukemia 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
  • Slides or tissue blocks from either initial diagnosis or relapse must be available for central review (if tissue blocks or slides are unavailable, the study chair must be notified prior to study enrollment)
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age

    • 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
  • For patients with solid tumors without known bone marrow involvement including patients who are status post-stem cell transplantation:

    • Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3
    • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
  • For patients with solid tumors with known bone marrow metastatic disease:

    • These patients are eligible for study provided they meet the blood count criteria above and are not known to be refractory to red cell or platelet transfusions
  • For patients with leukemia (part B):

    • Blood counts are not required to be normal prior to enrollment on this trial, however, platelet count has to be >= 20,000/mm^3 (may receive platelet transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min^2 OR a serum creatinine based on age/gender as follows:

    • =< 0.6 mg/dL (for patients 1 to < 2 years old)
    • =< 0.8 mg/dL (for patients 2 to < 6 years old)
    • =< 1 mg/dL (for patients 6 to < 10 years old)
    • =< 1.2 mg/dL (for patients 10 to < 13 years old)
    • =< 1.4 mg/dL (for female patients >= 13 years old)
    • =< 1.5 mg/dL (for male patients 13 to < 16 years old)
    • =<1.7 mg/dL (for male patients >= 16 years old)
  • Bilirubin (sum of unconjugated plus conjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (aspartate aminotransferase [ALT]) =< 110 U/L for patients with solid tumors OR SGPT (ALT) =< 225 U/L for patients with leukemias (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin >= 2 g/dL
  • QTc =< 450 msec
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients must be able to swallow whole tablets

    • Nasogastric or gastrostomy (G)-tube administration is not allowed
  • Patients must have a body surface area (BSA) > 0.5 m^2 when enrolling on dose levels 0 or 1 of the every other day schedule

    • No 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
  • Patients with seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] v4) resulting from prior therapy must be =< grade 2
  • 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
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
  • Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
  • 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 with leukemia 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
    • Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of MK-2206
  • At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur (the duration of this interval must be discussed with the study chair)
  • At least 7 days after the last dose of a biologic agent

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur (the duration of this interval must be discussed with the study chair)
  • At least 6 weeks since the completion of any type of immunotherapy (e.g., tumor vaccines)
  • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
  • At least 2 weeks for local palliative radiation therapy (XRT) (small port); >= 24 weeks must have elapsed if prior total body irradiation (TBI), craniospinal XRT, or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
  • No evidence of active graft vs host disease and >= 8 weeks must have elapsed since transplant or stem cell infusion without TBI
  • At least 3 months since bone marrow transplantation
  • 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 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
  • Other concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy, or biologic therapy may NOT be administered to patients receiving study drug
Both
1 Year to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01231919
NCI-2011-02612, NCI-2011-02612, CDR0000687929, COG-ADVL1013, ADVL1013, ADVL1013, U01CA097452
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Maryam Fouladi COG Phase I Consortium
National Cancer Institute (NCI)
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP