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Selumetinib in Cancers With BRAF Mutations

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ClinicalTrials.gov Identifier: NCT00888134
Recruitment Status : Completed
First Posted : April 27, 2009
Results First Posted : January 15, 2016
Last Update Posted : January 15, 2016
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
Condition Adult Solid Neoplasm
Intervention Drug: Selumetinib
Enrollment 28
Recruitment Details  
Pre-assignment Details Participants 'complete' the treatment period if they ended their treatment for disease progression, unacceptable toxicity, withdrawal of consent, or intercurrent illness. Those participants who completed treatment then enter a follow-up period when they are followed until death or lost-to-follow-up.
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Period Title: Treatment With Study Drug
Started 28
Completed 27 [1]
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
[1]
21 had progressive disease; 5 had unacceptable toxicity; 1 finished treatment
Period Title: Follow-up
Started 27
Completed 26 [1]
Not Completed 1
Reason Not Completed
being followed for long-term survival             1
[1]
23 died; 3 were lost-to-follow-up
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
<=18 years
0
   0.0%
Between 18 and 65 years
19
  67.9%
>=65 years
9
  32.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female
17
  60.7%
Male
11
  39.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
27
  96.4%
Unknown or Not Reported
1
   3.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   3.6%
White
27
  96.4%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 28 participants
28
Type of cancer  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants
Non small-cell lung cancer 14
Colon cancer 10
Other cancer 4
1.Primary Outcome
Title Objective Response Rate in Patients With Cancers Other Than Melanoma
Hide Description Percentage of participants achieving either complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, when compared with baseline) using CT (computed tomography) scans (which are done every 6 weeks).
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description:

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: percentage of participants
0
2.Secondary Outcome
Title AKT Pathway Activity
Hide Description Correlation between response to AZD6244 and mutational analysis of AKT pathway (an intracellular signaling pathway important in regulating the cell cycle)
Time Frame Up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Samples and data were not collected for this outcome.
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description:

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers
Hide Description Percentage of participants with either colon cancer or non-small cell lung cancer achieving either complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, when compared with baseline) using CT (computed tomography) scans.
Time Frame Up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description:

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
0
4.Secondary Outcome
Title Progression-free Survival
Hide Description Reported as percentage of participants alive and progression free at 4-months. Will be estimated using Kaplan-Meier survival curves. Confidence intervals will be calculated and reported.
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description:

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Selumetinib: Given PO

Overall Number of Participants Analyzed 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.4
(8.7 to 37.8)
5.Secondary Outcome
Title Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip
Hide Description [Not Specified]
Time Frame Up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Samples and data were not collected for this outcome.
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description:

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events experienced by participants will be followed for 30 days after participant stops treatment. (if ongoing beyond 30 days, they were contacted by the study team until the event resolved)
Adverse Event Reporting Description Participants were seen every 3 weeks during study treatment for physical exam, vital signs and laboratory assessments.
 
Arm/Group Title Treatment (Selumetinib)
Hide Arm/Group Description

Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Given PO

All-Cause Mortality
Treatment (Selumetinib)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Selumetinib)
Affected / at Risk (%)
Total   17/28 (60.71%) 
Endocrine disorders   
hypothyroidism  1  1/28 (3.57%) 
Eye disorders   
increased intraocular pressure  1  1/28 (3.57%) 
blurry vision  1  2/28 (7.14%) 
retinopathy  1  1/28 (3.57%) 
Gastrointestinal disorders   
Fistula  1  1/28 (3.57%) 
Abdominal Pain  1  1/28 (3.57%) 
malignant ascites  1  1/28 (3.57%) 
ileus  1  1/28 (3.57%) 
General disorders   
fatigue  1  1/28 (3.57%) 
Infections and infestations   
pulmonary / URT infection  1  1/28 (3.57%) 
Metabolism and nutrition disorders   
SGPT  1  3/28 (10.71%) 
SGOT  1  1/28 (3.57%) 
hypoalbuminemia  1  1/28 (3.57%) 
Musculoskeletal and connective tissue disorders   
joint pain  1  1/28 (3.57%) 
muscle pain  1  1/28 (3.57%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
fatal progressive disease  1  3/28 (10.71%) 
Nervous system disorders   
dizziness  1  1/28 (3.57%) 
Psychiatric disorders   
confusion  1  1/28 (3.57%) 
mental status changes  1  1/28 (3.57%) 
Respiratory, thoracic and mediastinal disorders   
dyspnea  1  2/28 (7.14%) 
Skin and subcutaneous tissue disorders   
dry skin  1  1/28 (3.57%) 
skin infection  1  2/28 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE V 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Selumetinib)
Affected / at Risk (%)
Total   28/28 (100.00%) 
Blood and lymphatic system disorders   
hemoglobin - low  1  19/28 (67.86%) 
leukocytes  1  2/28 (7.14%) 
lymphopenia  1  8/28 (28.57%) 
platelets  1  6/28 (21.43%) 
edema - head and neck  1  5/28 (17.86%) 
edema - limb  1  14/28 (50.00%) 
edema - trunk  1  2/28 (7.14%) 
Cardiac disorders   
hypertension  1  3/28 (10.71%) 
Ear and labyrinth disorders   
tinnitus  1  2/28 (7.14%) 
Eye disorders   
tearing  1  2/28 (7.14%) 
other  1 [1]  3/28 (10.71%) 
Gastrointestinal disorders   
anorexia  1  5/28 (17.86%) 
constipation  1  8/28 (28.57%) 
diarrhea  1  14/28 (50.00%) 
dry mouth  1  3/28 (10.71%) 
fistula  1  2/28 (7.14%) 
mucositis  1  4/28 (14.29%) 
nausea  1  15/28 (53.57%) 
taste disturbance  1  2/28 (7.14%) 
vomiting  1  13/28 (46.43%) 
hemorrhage - anus  1  2/28 (7.14%) 
abdominal pain  1  8/28 (28.57%) 
other  1 [1]  3/28 (10.71%) 
General disorders   
fatigue  1  19/28 (67.86%) 
fever (without neutropenia)  1  2/28 (7.14%) 
Infections and infestations   
infection  1  5/28 (17.86%) 
Investigations   
INR  1  3/28 (10.71%) 
PTT  1  3/28 (10.71%) 
Metabolism and nutrition disorders   
hypoalbuminemia  1  16/28 (57.14%) 
alkaline phosphatase  1  17/28 (60.71%) 
SGPT  1  10/28 (35.71%) 
SGOT  1  21/28 (75.00%) 
bicarbonate  1  4/28 (14.29%) 
bilirubin  1  3/28 (10.71%) 
hypocalcemia  1  7/28 (25.00%) 
hypercholesterolemia  1  2/28 (7.14%) 
creatinine  1  3/28 (10.71%) 
hyperglycemia  1  20/28 (71.43%) 
hypoglycemia  1  2/28 (7.14%) 
hypermagnesemia  1  3/28 (10.71%) 
hypomagnesemia  1  8/28 (28.57%) 
hypophosphatemia  1  3/28 (10.71%) 
hyperkalemia  1  6/28 (21.43%) 
hypokalemia  1  7/28 (25.00%) 
hyponatremia  1  8/28 (28.57%) 
other  1 [1]  5/28 (17.86%) 
Musculoskeletal and connective tissue disorders   
back pain  1  7/28 (25.00%) 
extremity - limb pain  1  3/28 (10.71%) 
joint pain  1  2/28 (7.14%) 
Nervous system disorders   
dizziness  1  6/28 (21.43%) 
neuropathy - sensory  1  7/28 (25.00%) 
headache  1  3/28 (10.71%) 
Psychiatric disorders   
insomnia  1  5/28 (17.86%) 
depression  1  4/28 (14.29%) 
Respiratory, thoracic and mediastinal disorders   
allergic rhinitis  1  2/28 (7.14%) 
hemorrhage - nose  1  2/28 (7.14%) 
cough  1  13/28 (46.43%) 
dyspnea  1  10/28 (35.71%) 
voice changes/ dysarthria  1  4/28 (14.29%) 
other  1 [1]  4/28 (14.29%) 
Skin and subcutaneous tissue disorders   
dry skin  1  3/28 (10.71%) 
nail changes  1  3/28 (10.71%) 
pruritis  1  4/28 (14.29%) 
rash/desquamation  1  6/28 (21.43%) 
rash: acneiform  1  19/28 (67.86%) 
rash: erythema multiforme  1  2/28 (7.14%) 
skin - other  1  4/28 (14.29%) 
other  1 [2]  4/28 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE V 3.0
[1]
AEs not falling into CTCAE categories
[2]
AEs not falling into pre-defined CTCAE categories
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
Name/Title: Donald P. Lawrence
Organization: Massachusetts General Hospital
Phone: 617-643-3614
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00888134     History of Changes
Other Study ID Numbers: NCI-2013-00576
NCI-2013-00576 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA006516 ( U.S. NIH Grant/Contract )
U01CA062490 ( U.S. NIH Grant/Contract )
CDR642346
N01CM62206 ( U.S. NIH Grant/Contract )
09-005 ( Other Identifier: Massachusetts General Hospital Cancer Center )
8281 ( Other Identifier: CTEP )
First Submitted: April 23, 2009
First Posted: April 27, 2009
Results First Submitted: December 10, 2015
Results First Posted: January 15, 2016
Last Update Posted: January 15, 2016