Trial Outcomes & Findings for AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma (NCT NCT01085214)
NCT ID: NCT01085214
Last Updated: 2015-08-19
Results Overview
Overall Response: Stringent Complete Response (sCR) + Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Up to 2 years
Results posted on
2015-08-19
Participant Flow
Participants were enrolled at 6 sites in the United States, from April 1, 2010 through July 28, 2011.
Participant milestones
| Measure |
AZD6244 (Selumetinib) Treatment
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 Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
AZD6244 (Selumetinib) Treatment
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 Study
Alternate treatment required
|
1
|
Baseline Characteristics
AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma
Baseline characteristics by cohort
| Measure |
AZD6244 (Selumetinib) Treatment
n=37 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
19 Participants
n=5 Participants
|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: All participants who received study treatment
Overall Response: Stringent Complete Response (sCR) + Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR).
Outcome measures
| Measure |
AZD6244 (Selumetinib) Treatment
n=36 Participants
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 Response Rate
Response: Total
|
2 participants
|
|
Overall Response Rate
Response: sCR
|
0 participants
|
|
Overall Response Rate
Response: CR
|
0 participants
|
|
Overall Response Rate
Response: VGPR
|
1 participants
|
|
Overall Response Rate
Response: PR
|
1 participants
|
|
Overall Response Rate
Other Status: Stable Disease
|
17 participants
|
|
Overall Response Rate
Other Status: Progressive Disease
|
13 participants
|
|
Overall Response Rate
Could not be assessed
|
4 participants
|
SECONDARY outcome
Timeframe: From response to disease progression or death, assessed up to 2 yearsPopulation: All participants with response
Mean duration of response in months. Estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
AZD6244 (Selumetinib) Treatment
n=2 Participants
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.
|
|---|---|
|
Duration of Response
|
4.95 months
Interval 4.83 to 5.06
|
SECONDARY outcome
Timeframe: 1 year, 11 monthsPopulation: All participants who received study treatment
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).
Outcome measures
| Measure |
AZD6244 (Selumetinib) Treatment
n=36 Participants
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.
|
|---|---|
|
Incidence of Toxicity That May Be Treatment Emergent
Non-Hematologic - Any Grade 3
|
14 participants
|
|
Incidence of Toxicity That May Be Treatment Emergent
Hematologic - Any Grade 3
|
6 participants
|
|
Incidence of Toxicity That May Be Treatment Emergent
Hematologic - Any Grade 4
|
2 participants
|
|
Incidence of Toxicity That May Be Treatment Emergent
Hematologic - Any Grade 5
|
0 participants
|
|
Incidence of Toxicity That May Be Treatment Emergent
Non-Hematologic - Any Grade 4
|
1 participants
|
|
Incidence of Toxicity That May Be Treatment Emergent
Non-Hematologic - Any Grade 5
|
3 participants
|
SECONDARY outcome
Timeframe: From registration to progression or death, assessed up to 2 yearsPopulation: All participants who received study treatment
Median PFS in months. Progressive Disease (PD): Increase of \>= 25% from baseline. Estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
AZD6244 (Selumetinib) Treatment
n=36 Participants
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.
|
|---|---|
|
Progression Free Survival (PFS)
|
3.52 months
Interval 2.6 to 5.92
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to up to 20-30 hours after receiving the first dose of AZD6244Effect of AZD6244 on the bone marrow microenvironment in MM.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 20-30 hours after receiving the first dose of selumetinibThe 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).
Outcome measures
Outcome data not reported
Adverse Events
AZD6244 (Selumetinib) Treatment
Serious events: 23 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AZD6244 (Selumetinib) Treatment
n=36 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Gastrointestinal disorders
Diarrhea
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Gastrointestinal disorders
Nausea
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
General disorders
Death, NOS
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
General disorders
Flu like symptoms
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
General disorders
Pain
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Hepatobiliary disorders
Hepatic failure
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Infections and infestations
Sepsis
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Infections and infestations
Skin infection
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Injury, poisoning and procedural complications
Fall
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Injury, poisoning and procedural complications
Fracture
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Investigations
Alanine aminotransferase increased
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Investigations
Aspartate aminotransferase increased
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Investigations
CPK increased
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Investigations
INR increased
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Investigations
Neutrophil count decreased
|
13.9%
5/36 • Number of events 7 • 1 year, 11 months
|
|
Investigations
Platelet count decreased
|
13.9%
5/36 • Number of events 5 • 1 year, 11 months
|
|
Investigations
White blood cell decreased
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Psychiatric disorders
Confusion
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Renal and urinary disorders
Acute kidney injury
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, Acute renal failure
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Reproductive system and breast disorders
Vaginal inflammation
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral
|
2.8%
1/36 • Number of events 1 • 1 year, 11 months
|
|
Vascular disorders
Hypotension
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
Other adverse events
| Measure |
AZD6244 (Selumetinib) Treatment
n=36 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
75.0%
27/36 • Number of events 46 • 1 year, 11 months
|
|
Gastrointestinal disorders
Nausea
|
30.6%
11/36 • Number of events 15 • 1 year, 11 months
|
|
Gastrointestinal disorders
Vomiting
|
30.6%
11/36 • Number of events 16 • 1 year, 11 months
|
|
Gastrointestinal disorders
Abdominal pain
|
11.1%
4/36 • Number of events 5 • 1 year, 11 months
|
|
Gastrointestinal disorders
Dry mouth
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
General disorders
Fatigue
|
50.0%
18/36 • Number of events 29 • 1 year, 11 months
|
|
General disorders
Edema, limbs
|
44.4%
16/36 • Number of events 20 • 1 year, 11 months
|
|
General disorders
Edema, face
|
19.4%
7/36 • Number of events 7 • 1 year, 11 months
|
|
General disorders
Pain
|
11.1%
4/36 • Number of events 4 • 1 year, 11 months
|
|
General disorders
Fever
|
11.1%
4/36 • Number of events 4 • 1 year, 11 months
|
|
General disorders
Localized edema
|
11.1%
4/36 • Number of events 6 • 1 year, 11 months
|
|
General disorders
Chills
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Investigations
Aspartate aminotransferase increased
|
38.9%
14/36 • Number of events 18 • 1 year, 11 months
|
|
Investigations
Neutrophil count decreased
|
33.3%
12/36 • Number of events 33 • 1 year, 11 months
|
|
Investigations
White blood cell decreased
|
33.3%
12/36 • Number of events 29 • 1 year, 11 months
|
|
Investigations
Platelet count decreased
|
27.8%
10/36 • Number of events 16 • 1 year, 11 months
|
|
Investigations
CPK increased
|
25.0%
9/36 • Number of events 12 • 1 year, 11 months
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
6/36 • Number of events 7 • 1 year, 11 months
|
|
Investigations
Creatinine increased
|
13.9%
5/36 • Number of events 5 • 1 year, 11 months
|
|
Investigations
Lymphocyte count decreased
|
13.9%
5/36 • Number of events 11 • 1 year, 11 months
|
|
Investigations
Alkaline phosphatase increased
|
8.3%
3/36 • Number of events 4 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
44.4%
16/36 • Number of events 27 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
25.0%
9/36 • Number of events 15 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
19.4%
7/36 • Number of events 12 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
19.4%
7/36 • Number of events 8 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
19.4%
7/36 • Number of events 9 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
13.9%
5/36 • Number of events 5 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
11.1%
4/36 • Number of events 5 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Anorexia
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.3%
3/36 • Number of events 4 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
47.2%
17/36 • Number of events 26 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
6/36 • Number of events 6 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
13.9%
5/36 • Number of events 8 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Periorbital edema
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Blood and lymphatic system disorders
Anemia
|
47.2%
17/36 • Number of events 27 • 1 year, 11 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.9%
5/36 • Number of events 6 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Infections and infestations
Sinusitis
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Infections and infestations
Upper respiratory infection
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
|
Nervous system disorders
Dizziness
|
11.1%
4/36 • Number of events 5 • 1 year, 11 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
11.1%
4/36 • Number of events 8 • 1 year, 11 months
|
|
Nervous system disorders
Headache
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Vascular disorders
Hypertension
|
22.2%
8/36 • Number of events 9 • 1 year, 11 months
|
|
Vascular disorders
Hypotension
|
5.6%
2/36 • Number of events 3 • 1 year, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
13.9%
5/36 • Number of events 6 • 1 year, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Psychiatric disorders
Insomnia
|
8.3%
3/36 • Number of events 3 • 1 year, 11 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
5.6%
2/36 • Number of events 2 • 1 year, 11 months
|
Additional Information
Steven Grant, M.D.
Massey Cancer Center, Virginia Commonwealth University
Phone: 804-828-5211
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60