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AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01085214
Recruitment Status : Completed
First Posted : March 11, 2010
Results First Posted : August 19, 2015
Last Update Posted : August 19, 2015
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies how well selumetinib works in treating patients with multiple myeloma, a type of cancer in which a specific protein is over active. Selumetinib may stop the growth of cancer cells by blocking this protein.

Condition or disease Intervention/treatment Phase
Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Other: Laboratory Biomarker Analysis Drug: Selumetinib Phase 2

Detailed Description:


I. To assess the response rate of AZD6244 (selumetinib) hydrogen sulfate capsules in patients with relapsed or refractory multiple myeloma (MM).


I. To evaluate the toxicity of AZD6244 in patients with MM. II. To estimate progression-free survival and duration of response to AZD6244. III. To test whether AZD6244 hydrogen sulfate capsules downregulate tumor cell phosphorylated mitogen-activated protein kinase (pERK)1/2.


Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD6244 in Multiple Myeloma
Study Start Date : March 2010
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Selumetinib

Arm Intervention/treatment
Experimental: AZD6244 (Selumetinib) Treatment
Participants receive AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Selumetinib
AZD6244 (Selumetinib), 75 mg was administered orally, twice a day, continuously for 28-day cycles
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 2 years ]
    Overall Response: Stringent Complete Response (sCR) + Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR).

Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: From response to disease progression or death, assessed up to 2 years ]
    Mean duration of response in months. Estimated using the method of Kaplan-Meier.

  2. Incidence of Toxicity That May Be Treatment Emergent [ Time Frame: 1 year, 11 months ]
    Participants with Grade 3, 4, and 5 toxicities possibly, probably, or definitely related to study treatment. Toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

  3. Progression Free Survival (PFS) [ Time Frame: From registration to progression or death, assessed up to 2 years ]
    Median PFS in months. Progressive Disease (PD): Increase of >= 25% from baseline. Estimated using the method of Kaplan-Meier.

Other Outcome Measures:
  1. Changes in Bone Marrow Microenvironment [ Time Frame: Baseline to up to 20-30 hours after receiving the first dose of AZD6244 ]
    Effect of AZD6244 on the bone marrow microenvironment in MM.

  2. Level of Key Regulators [ Time Frame: Up to 20-30 hours after receiving the first dose of selumetinib ]
    The level of key regulators of the MEK/MAPK and PI3K pathways and HSP90 and cell cycle regulators may determine the anti-tumor response to AZD6244 in vivo in multiple myeloma (MM).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed diagnosis of multiple myeloma with relapsed or refractory disease following at least two prior therapies
  • Measurable disease defined as:

    • Serum monoclonal protein >= 1 gm/dL or
    • Urine monoclonal protein of >= 200 mg/24 hours, or
    • Measurable free light chains by free light chain assay of >= 10 mg/dL with abnormal kappa to lambda free light chain ratio, or
    • Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest diameter to be recorded) >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan (for patients with lytic bone disease)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count: >= 1,000/μL (independent of blood cell growth factors)
  • Platelets: >= 75,000/μL (independent of blood cell growth factors or transfusion)
  • Total bilirubin: =< 1.5 x upper normal limit; however, patients with documented Gilbert's syndrome are eligible
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): < 2.5 x upper limit of normal (ULN)
  • Creatinine: < 3.0 x ULN
  • Known human immunodeficiency virus (HIV) infected patients meeting the following characteristics are eligible:

    • Cluster of differentiation (CD)4 cell count >= 500/mm^3
    • Meeting either of the following:

      • Willing to suspend antiretroviral therapy for duration of protocol therapy or
      • On stable regimen of combination antiretroviral therapy that does not include either zidovudine or stavudine for at least 12 weeks and without evidence of toxicity
    • No HIV-associated condition that defines acquired immunodeficiency syndrome (AIDS)
  • Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:

    • >= 6 months have elapsed since allogeneic transplant
    • No graft vs. host disease (GVHD) is present
    • Not currently on immunosuppressive therapy
  • Women of child-bearing potential must agree to use a medically accepted form of contraception prior to, during, and for four weeks following study treatment; men must agree to use a medically accepted form of contraception prior to, during, and for sixteen weeks following study treatment
  • Able and willing to provide a written informed consent
  • Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy
  • Pulse oximetry of >= 95% on room air

Exclusion Criteria:

  • Any concurrent condition or planned treatment that would compromise study objectives or represent an unacceptable patient risk, including but not limited to:

    • Planned concurrent treatment for multiple myeloma other than bisphosphonates; ongoing corticosteroids for indications other than multiple myeloma allowed as long as the dose does not exceed 60 mg of prednisone per day or equivalent
    • Persisting effects of any previous or ongoing treatment that might compromise delivery of study treatment or assessment of adverse events
    • Planned concurrent treatment with any other investigational agents
  • Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration
  • No other malignancy unless the patient has been disease-free for >= 1 year
  • Known multiple myeloma of central nervous system or leptomeninges
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
  • Previous mitogen activated protein kinase (MEK) inhibitor use
  • Uncontrolled hypertension, i.e., persistent blood pressure (BP) of >= 160/95
  • Significant cardiovascular disease (New York Heart Association class II, III or IV cardiac disease), hypertrophic cardiomegaly or restrictive cardiomyopathy, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia unstable or a need for anti-arrhythmic therapy (use of medication for atrial fibrillation is allowed, if stable for at least 3 months)
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or nursing
  • Left ventricular ejection fraction (LVEF) =< 45% by echocardiogram (ECHO) or multigated acquisition scan (MUGA) scan
  • Any requirement for supplemental oxygen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01085214

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United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
Mark O Hatfield-Warren Grant Magnuson Clinical Center
Bethesda, Maryland, United States, 20892
National Institutes of Health
Bethesda, Maryland, United States, 20892
United States, Montana
Billings Clinic Cancer Center
Billings, Montana, United States, 59107
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Steven Grant, M.D. Massey Cancer Center
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT01085214    
Other Study ID Numbers: NCI-2012-02929
NCI-2012-02929 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10-C-0079 ( Other Identifier: Moffitt Cancer Center )
8631 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
N01CM00100 ( U.S. NIH Grant/Contract )
N01CM62208 ( U.S. NIH Grant/Contract )
P30CA076292 ( U.S. NIH Grant/Contract )
First Posted: March 11, 2010    Key Record Dates
Results First Posted: August 19, 2015
Last Update Posted: August 19, 2015
Last Verified: May 2015
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases