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Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations

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ClinicalTrials.gov Identifier: NCT03040986
Recruitment Status : Completed
First Posted : February 2, 2017
Results First Posted : January 11, 2021
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions KRAS NP_004976.2:p.G12R
Stage III Pancreatic Cancer AJCC v6 and v7
Stage IV Pancreatic Cancer AJCC v6 and v7
Interventions Other: Laboratory Biomarker Analysis
Drug: Selumetinib Sulfate
Enrollment 8
Recruitment Details  
Pre-assignment Details 180 pts were not enrolled to the study. All pts who made contact to participate in the study all had KRAS G12R mutation testing thus pre-screening was not necessary. The 1st 8 pts who made contact with the study and were eligible were consented, enrolled and treated. No other pts were enrolled in the study per the statistical design in the protocol. As pre-specified, the study did not move into the second phase due to lack of efficacy.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity. Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 6 2
Completed 0 0
Not Completed 6 2
Reason Not Completed
Hospice             1             0
Adverse Event             2             1
Disease progression on study             3             1
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Total
Hide Arm/Group Description Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity. Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 6 2 8
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
  66.7%
2
 100.0%
6
  75.0%
>=65 years
2
  33.3%
0
   0.0%
2
  25.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 2 participants 8 participants
62  (8.99) 59  (7.07) 60.5  (8.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
Female
2
  33.3%
2
 100.0%
4
  50.0%
Male
4
  66.7%
0
   0.0%
4
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
Hispanic or Latino
0
   0.0%
1
  50.0%
1
  12.5%
Not Hispanic or Latino
6
 100.0%
1
  50.0%
7
  87.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  16.7%
0
   0.0%
1
  12.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  16.7%
0
   0.0%
1
  12.5%
White
4
  66.7%
2
 100.0%
6
  75.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 2 participants 8 participants
6 2 8
Location of Primary Tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
Head/Body
4
  66.7%
1
  50.0%
5
  62.5%
Tail
2
  33.3%
1
  50.0%
3
  37.5%
Previous Treatments  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
Radiation
2
  33.3%
1
  50.0%
3
  37.5%
Surgery
3
  50.0%
2
 100.0%
5
  62.5%
Multiple agents systemic chemotherapy
6
 100.0%
2
 100.0%
8
 100.0%
Number of Previous Lines of Systemic Chemotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
1 1 0 1
2 2 1 3
≥3 3 1 4
Number of Metastatic Sites (involved organs)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 8 participants
1 2 0 2
2 1 2 3
≥3 3 0 3
1.Primary Outcome
Title Proportion of Participants With an Objective Response (Partial Response + Complete Response)
Hide Description Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm (<1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Approximately 1-8.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Number
Unit of Measure: Proportion of participants
Partial Response 0 0
Complete Response 0 0
2.Secondary Outcome
Title Median Progression-free Survival (PFS)
Hide Description PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.
Time Frame From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants are grouped together as pre-specified in the protocol for this outcome measure.
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants that received 75mg selumetinib sulfate by mouth (PO) twice daily (BID); and 75mg Selumetinib sulfate twice daily followed by 50mg twice daily.
Overall Number of Participants Analyzed 8
Median (95% Confidence Interval)
Unit of Measure: Months
3.0
(0.8 to 8.2)
3.Secondary Outcome
Title Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib
Hide Description Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.
Time Frame Date treatment consent signed to date off study, approximately 25 months and 6 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Probably Attributable: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Number
Unit of Measure: Adverse events
Probably: Grade 3 Hypertension 2 0
Probably: Grade 3 Pancreatitis 1 0
Definitely: Grade 3 Alanine aminotransferase increased 0 2
Definitely: Grade 3 Dyspnea 1 0
Definitely: Grade 3 Heart failure 1 0
Definitely: Grade 3 Hypertension 0 1
4.Secondary Outcome
Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Hide Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 25 months and 6 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
2
 100.0%
5.Secondary Outcome
Title Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)
Hide Description Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not done because only 1 out of the 8 enrolled participants agreed to undergo biopsy while on treatment. Tumoral biopsies were not mandatory but optional for participants enrolled onto the study. Because only one biopsy specimen was obtained, on the discretion of the PI, no analysis and no comparisons were performed.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Predictive Biomarkers for Response to Selumetinib
Hide Description Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be > and < 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels > 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels < 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Since no responses were observed in either Arm/Group, the planned correlation was not conducted for this outcome measure.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Longitudinal Biomarker Measuring Response to Treatment
Hide Description Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.
Time Frame start of treatment every (q)2 weeks, up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not done because of the lack of ctDNA copy number determinations in participants on-treatment compared to pre-treatment levels in the participants whose ctDNA levels were longitudinally evaluable. No variant profiling of baseline tumoral tissues was performed.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Change in the Somatic Circulating Tumor Deoxyribonucleic Acid (ctDNA) Mutation Profile and Its Correlation With Clinical Outcome
Hide Description The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.
Time Frame Baseline up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No other somatic variants in ctDNA other than the KRAS allele were analyzed because the only available droplet digital PCR (ddPCR) assay was the one for the KRAS allele. Thus, the planned analysis change in the somatic ctDNA mutation profile and its correlation with clinical outcome was not conducted.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA)
Hide Description ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.
Time Frame Baseline and the last KRAS value before the participant came off treatment, approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Mean (Standard Deviation)
Unit of Measure: copies
Baseline 2584  (2242) 1556  (480)
Last recorded value 6607  (6067) 1542  (586)
10.Secondary Outcome
Title Overall Percentage Change (%) of Copies KRAS Wild Type Allele
Hide Description Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.
Time Frame Approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Number
Unit of Measure: Percentage change
156 -1
11.Secondary Outcome
Title Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA)
Hide Description Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.
Time Frame Baseline and last recorded value while on treatment, approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Mean (Standard Deviation)
Unit of Measure: copies
Baseline 3.33  (3.79) 0  (0)
On Treatment 10.33  (15) 1.6  (0.8)
12.Secondary Outcome
Title Overall Percentage Change of Copies KRAS Mutant Type Allele
Hide Description Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.
Time Frame Approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Number
Unit of Measure: Percentage change
210 NA [1] 
[1]
The percentage was not calculable because the denominator had a value of 0.
13.Secondary Outcome
Title Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA
Hide Description This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.
Time Frame Between baseline and last recorded value while on-treatment, approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Mean (Standard Deviation)
Unit of Measure: Percentage
Baseline 7.5  (8.7891979156235) 0  (0)
Last recorded value 9.33  (14.185281887302) 8.5  (8.5)
14.Secondary Outcome
Title Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
Hide Description Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment
Time Frame Approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 2
Measure Type: Number
Unit of Measure: Percentage change
19.6 8.5
15.Secondary Outcome
Title Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline
Hide Description Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).
Time Frame Baseline and last recorded value while on-treatment, approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 3 2
Mean (Standard Deviation)
Unit of Measure: Variant Allele Fraction (VAF, %) of KRAS
Baseline 0  (0) 0  (0)
Last recorded value 0  (0) 8.5  (8.5)
16.Secondary Outcome
Title Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline
Hide Description Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).
Time Frame Approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 3 2
Measure Type: Number
Unit of Measure: Percentage change
0 8.5
17.Secondary Outcome
Title Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment
Hide Description This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline > 0%).
Time Frame Baseline and last recorded value after treatment, approximately 1- 8.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline and after treatment
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: Percentage change
Baseline 18  (6)
Last recorded value 28  (9)
18.Secondary Outcome
Title Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment
Hide Description Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.
Time Frame Approximately 1- 8.2 months.
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Hide Analysis Population Description
Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description:
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2 0
Measure Type: Number
Unit of Measure: Percentage change
60.9
Time Frame Date treatment consent signed to date off study, approximately 25 months and 6 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Hide Arm/Group Description Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity. Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)      2/2 (100.00%)    
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Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/6 (50.00%)      0/2 (0.00%)    
Cardiac disorders     
Heart failure  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Gastrointestinal disorders     
Colonic obstruction  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Pancreatitis  1  1/6 (16.67%)  2 0/2 (0.00%)  0
Hepatobiliary disorders     
Gallbladder obstruction  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Infections and infestations     
Gallbladder infection  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Investigations     
Lipase increased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Serum amylase increased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Psychiatric disorders     
Confusion  1  1/6 (16.67%)  1 0/2 (0.00%)  0
1
Term from vocabulary, CTCAE (5.0)
Indicates events were collected by systematic assessment
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Frequency Threshold for Reporting Other Adverse Events 0%
Dose Level 0: 75mg Selumetinib Sulfate Twice Daily 75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  3/6 (50.00%)  5 0/2 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  0/6 (0.00%)  0 1/2 (50.00%)  2
Abdominal pain  1  3/6 (50.00%)  4 0/2 (0.00%)  0
Ascites  1  1/6 (16.67%)  2 0/2 (0.00%)  0
Bloating  1  2/6 (33.33%)  2 0/2 (0.00%)  0
Diarrhea  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Dry mouth  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Dysphagia  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Flatulence  1  0/6 (0.00%)  0 2/2 (100.00%)  2
Gastroesophageal reflux disease  1  0/6 (0.00%)  0 1/2 (50.00%)  1
Nausea  1  3/6 (50.00%)  4 0/2 (0.00%)  0
Pancreatitis  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Vomiting  1  2/6 (33.33%)  2 0/2 (0.00%)  0
General disorders     
Edema face  1  0/6 (0.00%)  0 1/2 (50.00%)  1
Edema limbs  1  5/6 (83.33%)  6 1/2 (50.00%)  1
Edema trunk  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Fatigue  1  4/6 (66.67%)  5 1/2 (50.00%)  1
Fever  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Generalized muscle weakness  1  2/6 (33.33%)  2 0/2 (0.00%)  0
Malaise  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Infections and infestations     
Biliary tract infection  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Peritoneal infection  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  3/6 (50.00%)  4 2/2 (100.00%)  10
Alkaline phosphatase increased  1  3/6 (50.00%)  5 0/2 (0.00%)  0
Aspartate aminotransferase increased  1  6/6 (100.00%)  9 2/2 (100.00%)  5
Blood bilirubin increased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
CPK increased  1  2/6 (33.33%)  3 0/2 (0.00%)  0
Creatinine increased  1  2/6 (33.33%)  4 0/2 (0.00%)  0
Lipase increased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Lymphocyte count decreased  1  2/6 (33.33%)  4 0/2 (0.00%)  0
Neutrophil count decreased  1  1/6 (16.67%)  1 1/2 (50.00%)  1
Platelet count decreased  1  0/6 (0.00%)  0 1/2 (50.00%)  1
Serum amylase increased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Weight loss  1  1/6 (16.67%)  1 0/2 (0.00%)  0
White blood cell decreased  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia  1  3/6 (50.00%)  3 0/2 (0.00%)  0
Glucose intolerance  1  1/6 (16.67%)  2 0/2 (0.00%)  0
Hypercalcemia  1  0/6 (0.00%)  0 1/2 (50.00%)  1
Hyperglycemia  1  1/6 (16.67%)  1 1/2 (50.00%)  1
Hypoalbuminemia  1  5/6 (83.33%)  7 1/2 (50.00%)  1
Hypocalcemia  1  2/6 (33.33%)  2 1/2 (50.00%)  1
Hypokalemia  1  2/6 (33.33%)  2 0/2 (0.00%)  0
Hypomagnesemia  1  1/6 (16.67%)  2 0/2 (0.00%)  0
Hyponatremia  1  2/6 (33.33%)  2 0/2 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Muscle weakness trunk  1  0/6 (0.00%)  0 1/2 (50.00%)  1
Musculoskeletal and connective tissue disorder - Other, muscle spasm  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Neck pain  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Nervous system disorders     
Dizziness  1  2/6 (33.33%)  4 0/2 (0.00%)  0
Dysgeusia  1  1/6 (16.67%)  2 0/2 (0.00%)  0
Paresthesia  1  1/6 (16.67%)  3 1/2 (50.00%)  1
Renal and urinary disorders     
Renal and urinary disorders - Other, Dysuria  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Urinary tract obstruction  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Urine discoloration  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Cough  1  2/6 (33.33%)  2 0/2 (0.00%)  0
Dyspnea  1  3/6 (50.00%)  4 1/2 (50.00%)  1
Pleural effusion  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Postnasal drip  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Sore throat  1  1/6 (16.67%)  1 1/2 (50.00%)  1
Skin and subcutaneous tissue disorders     
Alopecia  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Pruritus  1  0/6 (0.00%)  0 2/2 (100.00%)  3
Rash acneiform  1  1/6 (16.67%)  1 0/2 (0.00%)  0
Rash maculo-papular  1  2/6 (33.33%)  2 2/2 (100.00%)  2
Vascular disorders     
Hypertension  1  4/6 (66.67%)  10 2/2 (100.00%)  5
Hypotension  1  1/6 (16.67%)  1 0/2 (0.00%)  0
1
Term from vocabulary, CTCAE (5.0)
Indicates events were collected by systematic assessment
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
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Name/Title: Dr. Udo Rudloff
Organization: National Cancer Institute
Phone: 240-760-6238
EMail: udo.rudloff@nih.gov
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03040986    
Other Study ID Numbers: NCI-2017-00118
NCI-2017-00118 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17C0144
10050 ( Other Identifier: National Cancer Institute LAO )
10050 ( Other Identifier: CTEP )
ZIABC011078 ( U.S. NIH Grant/Contract )
First Submitted: February 1, 2017
First Posted: February 2, 2017
Results First Submitted: October 18, 2020
Results First Posted: January 11, 2021
Last Update Posted: February 9, 2021