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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.
 
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)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Interventions Other: Laboratory Biomarker Analysis
Drug: Selumetinib
Enrollment 37
Recruitment Details Participants were enrolled at 6 sites in the United States, from April 1, 2010 through July 28, 2011.
Pre-assignment Details  
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 37
Completed 36
Not Completed 1
Reason Not Completed
Alternate treatment required             1
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
All participants enrolled.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
<=18 years
0
   0.0%
Between 18 and 65 years
18
  48.6%
>=65 years
19
  51.4%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
65
(43 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
19
  51.4%
Male
18
  48.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 37 participants
37
1.Primary Outcome
Title Overall Response Rate
Hide Description Overall Response: Stringent Complete Response (sCR) + Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR).
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received study treatment
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description:
Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: participants
Response: Total 2
Response: sCR 0
Response: CR 0
Response: VGPR 1
Response: PR 1
Other Status: Stable Disease 17
Other Status: Progressive Disease 13
Could not be assessed 4
2.Secondary Outcome
Title Duration of Response
Hide Description Mean duration of response in months. Estimated using the method of Kaplan-Meier.
Time Frame From response to disease progression or death, assessed up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with response
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description:
Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2
Mean (Full Range)
Unit of Measure: months
4.95
(4.83 to 5.06)
3.Secondary Outcome
Title Incidence of Toxicity That May Be Treatment Emergent
Hide Description 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).
Time Frame 1 year, 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received study treatment
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description:
Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: participants
Hematologic - Any Grade 3 6
Hematologic - Any Grade 4 2
Hematologic - Any Grade 5 0
Non-Hematologic - Any Grade 3 14
Non-Hematologic - Any Grade 4 1
Non-Hematologic - Any Grade 5 3
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Median PFS in months. Progressive Disease (PD): Increase of >= 25% from baseline. Estimated using the method of Kaplan-Meier.
Time Frame From registration to progression or death, assessed up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received study treatment
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description:
Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 36
Median (Full Range)
Unit of Measure: months
3.52
(2.60 to 5.92)
5.Other Pre-specified Outcome
Title Changes in Bone Marrow Microenvironment
Hide Description Effect of AZD6244 on the bone marrow microenvironment in MM.
Time Frame Baseline to up to 20-30 hours after receiving the first dose of AZD6244
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Level of Key Regulators
Hide Description 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).
Time Frame Up to 20-30 hours after receiving the first dose of selumetinib
Outcome Measure Data Not Reported
Time Frame 1 year, 11 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD6244 (Selumetinib) Treatment
Hide Arm/Group Description Participants received AZD6244 (Selumetinib) orally (PO) twice a day (BID) on days 1-28. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
AZD6244 (Selumetinib) Treatment
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AZD6244 (Selumetinib) Treatment
Affected / at Risk (%) # Events
Total   23/36 (63.89%)    
Blood and lymphatic system disorders   
Anemia  1  3/36 (8.33%)  3
Febrile neutropenia  1  1/36 (2.78%)  1
Gastrointestinal disorders   
Diarrhea  1  2/36 (5.56%)  2
Nausea  1  1/36 (2.78%)  1
General disorders   
Death, NOS  1  3/36 (8.33%)  3
Flu like symptoms  1  1/36 (2.78%)  1
Pain  1  1/36 (2.78%)  1
Hepatobiliary disorders   
Hepatic failure  1  1/36 (2.78%)  1
Infections and infestations   
Sepsis  1  3/36 (8.33%)  3
Skin infection  1  1/36 (2.78%)  1
Injury, poisoning and procedural complications   
Fall  1  1/36 (2.78%)  1
Fracture  1  1/36 (2.78%)  1
Investigations   
Alanine aminotransferase increased  1  1/36 (2.78%)  1
Aspartate aminotransferase increased  1  3/36 (8.33%)  3
CPK increased  1  3/36 (8.33%)  3
INR increased  1  1/36 (2.78%)  1
Neutrophil count decreased  1  5/36 (13.89%)  7
Platelet count decreased  1  5/36 (13.89%)  5
White blood cell decreased  1  1/36 (2.78%)  1
Metabolism and nutrition disorders   
Hypercalcemia  1  1/36 (2.78%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/36 (2.78%)  1
Generalized muscle weakness  1  1/36 (2.78%)  1
Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis  1  2/36 (5.56%)  2
Myalgia  1  2/36 (5.56%)  2
Nervous system disorders   
Peripheral sensory neuropathy  1  2/36 (5.56%)  2
Psychiatric disorders   
Confusion  1  1/36 (2.78%)  1
Renal and urinary disorders   
Acute kidney injury  1  3/36 (8.33%)  3
Renal and urinary disorders - Other, Acute renal failure  1  1/36 (2.78%)  1
Reproductive system and breast disorders   
Vaginal inflammation  1  1/36 (2.78%)  1
Respiratory, thoracic and mediastinal disorders   
Adult respiratory distress syndrome  1  1/36 (2.78%)  1
Skin and subcutaneous tissue disorders   
Pruritus  1  1/36 (2.78%)  1
Rash acneiform  1  1/36 (2.78%)  1
Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral  1  1/36 (2.78%)  1
Vascular disorders   
Hypotension  1  2/36 (5.56%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD6244 (Selumetinib) Treatment
Affected / at Risk (%) # Events
Total   35/36 (97.22%)    
Blood and lymphatic system disorders   
Anemia  1  17/36 (47.22%)  27
Blood and lymphatic system disorders - Other  1  2/36 (5.56%)  2
Gastrointestinal disorders   
Diarrhea  1  27/36 (75.00%)  46
Nausea  1  11/36 (30.56%)  15
Vomiting  1  11/36 (30.56%)  16
Abdominal pain  1  4/36 (11.11%)  5
Dry mouth  1  3/36 (8.33%)  3
Gastroesophageal reflux disease  1  2/36 (5.56%)  2
Gastrointestinal disorders - Other  1  2/36 (5.56%)  2
General disorders   
Fatigue  1  18/36 (50.00%)  29
Edema, limbs  1  16/36 (44.44%)  20
Edema, face  1  7/36 (19.44%)  7
Pain  1  4/36 (11.11%)  4
Fever  1  4/36 (11.11%)  4
Localized edema  1  4/36 (11.11%)  6
Chills  1  2/36 (5.56%)  2
Infections and infestations   
Sinusitis  1  2/36 (5.56%)  3
Upper respiratory infection  1  2/36 (5.56%)  2
Investigations   
Aspartate aminotransferase increased  1  14/36 (38.89%)  18
Neutrophil count decreased  1  12/36 (33.33%)  33
White blood cell decreased  1  12/36 (33.33%)  29
Platelet count decreased  1  10/36 (27.78%)  16
CPK increased  1  9/36 (25.00%)  12
Alanine aminotransferase increased  1  6/36 (16.67%)  7
Creatinine increased  1  5/36 (13.89%)  5
Lymphocyte count decreased  1  5/36 (13.89%)  11
Alkaline phosphatase increased  1  3/36 (8.33%)  4
Metabolism and nutrition disorders   
Hypoalbuminemia  1  16/36 (44.44%)  27
Hypomagnesemia  1  9/36 (25.00%)  15
Hypocalcemia  1  7/36 (19.44%)  12
Hyponatremia  1  7/36 (19.44%)  8
Hypophosphatemia  1  7/36 (19.44%)  9
Hypokalemia  1  5/36 (13.89%)  5
Hyperkalemia  1  4/36 (11.11%)  5
Anorexia  1  3/36 (8.33%)  3
Hypoglycemia  1  3/36 (8.33%)  4
Dehydration  1  2/36 (5.56%)  2
Hypercalcemia  1  2/36 (5.56%)  3
Hypernatremia  1  2/36 (5.56%)  2
Metabolism and nutrition disorders - Other  1  2/36 (5.56%)  2
Musculoskeletal and connective tissue disorders   
Back pain  1  5/36 (13.89%)  6
Myalgia  1  2/36 (5.56%)  3
Generalized muscle weakness  1  2/36 (5.56%)  3
Pain in extremity  1  3/36 (8.33%)  3
Arthralgia  1  2/36 (5.56%)  2
Nervous system disorders   
Dizziness  1  4/36 (11.11%)  5
Peripheral sensory neuropathy  1  4/36 (11.11%)  8
Headache  1  2/36 (5.56%)  3
Psychiatric disorders   
Insomnia  1  3/36 (8.33%)  3
Renal and urinary disorders   
Renal and urinary disorders - Other  1  2/36 (5.56%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  5/36 (13.89%)  6
Cough  1  3/36 (8.33%)  3
Skin and subcutaneous tissue disorders   
Rash acneiform  1  17/36 (47.22%)  26
Dry skin  1  6/36 (16.67%)  6
Skin and subcutaneous tissue disorders - Other  1  5/36 (13.89%)  8
Periorbital edema  1  3/36 (8.33%)  3
Skin hypopigmentation  1  3/36 (8.33%)  3
Vascular disorders   
Hypertension  1  8/36 (22.22%)  9
Hypotension  1  2/36 (5.56%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Steven Grant, M.D.
Organization: Massey Cancer Center, Virginia Commonwealth University
Phone: 804-828-5211
EMail: stgrant@vcu.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01085214     History of Changes
Other Study ID Numbers: 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 )
First Submitted: March 10, 2010
First Posted: March 11, 2010
Results First Submitted: July 24, 2015
Results First Posted: August 19, 2015
Last Update Posted: August 19, 2015