AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma

NCT01085214 | Completed Phase 2 Results

• 9 other identifiers: NCI-2012-02929CDR669144NCI-863110-C-00798631N01CM00071N01CM00100N01CM62208P30CA076292
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 9

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall Response: Stringent Complete Response (sCR) + Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR).

  Up to 2 years

Secondary Outcomes (3)

• Duration of Response

  From response to disease progression or death, assessed up to 2 years

• Incidence of Toxicity That May Be Treatment Emergent

  1 year, 11 months

• Progression Free Survival (PFS)

  From registration to progression or death, assessed up to 2 years

Other Outcomes (2)

• Changes in Bone Marrow Microenvironment

  Baseline to up to 20-30 hours after receiving the first dose of AZD6244

• Level of Key Regulators

  Up to 20-30 hours after receiving the first dose of selumetinib

Study Arms (1)

AZD6244 (Selumetinib) Treatment

EXPERIMENTAL

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; Drug: Selumetinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

AZD6244 (Selumetinib) Treatment

Selumetinib DRUG

AZD6244 (Selumetinib), 75 mg was administered orally, twice a day, continuously for 28-day cycles

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

AZD6244 (Selumetinib) Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59107, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Steven Grant, M.D.
• Organization: Massey Cancer Center, Virginia Commonwealth University

stgrant@vcu.edu

804-828-5211

Study Officials

• Steven Grant, M.D.

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2010
• First Posted: March 11, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: August 19, 2015
• Results First Posted: August 19, 2015

Record last verified: 2015-05

Locations

US (9)