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AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01085214
Recruitment Status : Completed
First Posted : March 11, 2010
Results First Posted : August 19, 2015
Last Update Posted : August 19, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 10, 2010
First Posted Date  ICMJE March 11, 2010
Results First Submitted Date  ICMJE July 24, 2015
Results First Posted Date  ICMJE August 19, 2015
Last Update Posted Date August 19, 2015
Study Start Date  ICMJE March 2010
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2015)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2010)
To assess the response rate of AZD6244 hydrogen sulfate capsules in patients with relapsed or refractory MM. [ Time Frame: Beginning after 8 cycles (about 8 months per patient) ]
Change History Complete list of historical versions of study NCT01085214 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2015)
  • 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.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2010)
  • To evaluate the toxicity of AZD6244 in patients with MM [ Time Frame: Beginning after 8 cycles (about 8 months per patient) ]
  • To estimate time to progression and duration of response to AZD6244 [ Time Frame: Beginning after 8 cycles (about 8 months per patient) ]
  • To test whether AZD6244 hydrogen sulfate capsules downregulates tumor cell pERK1/2. [ Time Frame: Beginning after 8 cycles (about 8 months per patient) ]
Current Other Pre-specified Outcome Measures
 (submitted: May 14, 2015)
  • 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.
  • 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).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma
Official Title  ICMJE A Phase 2 Study of AZD6244 in Multiple Myeloma
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.
Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Selumetinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 10, 2010)
37
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01085214
Other Study ID Numbers  ICMJE NCI-2012-02929
NCI-2012-02929 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR669144
NCI-8631
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 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Steven Grant, M.D. Massey Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date May 2015

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