Selumetinib in Treating Patients With Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01085214
First received: March 10, 2010
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to find out what effects, good and/or bad, AZD6244 has on participants and their multiple myeloma. In some types of cancer such as myeloma, a protein called MEK is overactive. This protein is important for cancer cells to be able to reproduce and survive. Because AZD6244 prevents MEK from working properly, it may keep cancer cells from growing and living, so cancer may shrink or its growth may slow down. There is no guarantee, however, that this will happen to the patient's cancer if they join this study.


Condition Intervention Phase
Refractory Multiple Myeloma
Drug: selumetinib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD6244 in Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response (sCR+CR++VGPR+PR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity, graded using the NCI CTCAE [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Tabulated by category and grade.

  • Progression-free survival [ Time Frame: From registration to progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Duration of response [ Time Frame: From response to disease progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.


Enrollment: 36
Study Start Date: March 2010
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (selumetinib)
Patients receive selumetinib orally BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: selumetinib
Given orally
Other Names:
  • ARRY-142886
  • AZD6244
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the response rate of AZD6244 hydrogen sulfate capsules in patients with relapsed or refractory 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 pERK1/2.

OUTLINE:

Patients receive selumetinib orally 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 CT scan (for patients with lytic bone disease)
  • 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
  • AST(SGOT)/ALT(SGPT): < 2.5 x ULN
  • Creatinine: < 3.0 x ULN
  • Known HIV infected patients meeting the following characteristics are eligible:

    • CD4 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 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 60mg 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 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
  • LVEF =< 45% by ECHO or MUGA scan
  • Any requirement for supplemental oxygen
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085214

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
National Institutes of Health
Bethesda, Maryland, United States, 20892
United States, Montana
Billings Clinic
Billings, Montana, United States, 59107-7000
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Grant H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01085214     History of Changes
Other Study ID Numbers: NCI-2012-02929, NCI-2012-02929, CDR669144, NCI-8631, 8631, P30CA076292, N01CM00100, N01CM00071
Study First Received: March 10, 2010
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 14, 2014