Clinical trial NCT01085214: AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma
Official title: A Phase 2 Study of AZD6244 in Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-03-11
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Duration of Response
timeFrame: From response to disease progression or death, assessed up to 2 years
measure: Incidence of Toxicity That May Be Treatment Emergent
timeFrame: 1 year, 11 months
measure: Progression Free Survival (PFS)
timeFrame: From registration to progression or death, assessed up to 2 years
Other outcomes:
measure: Changes in Bone Marrow Microenvironment
timeFrame: Baseline to up to 20-30 hours after receiving the first dose of AZD6244
measure: Level of Key Regulators
timeFrame: Up to 20-30 hours after receiving the first dose of selumetinib
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Mark O Hatfield-Warren Grant Magnuson Clinical Center
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Steven Grant, M.D.
role: PRINCIPAL_INVESTIGATOR
References: