Trial Outcomes & Findings for Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery (NCT NCT00553332)

Last Updated: 2016-04-22

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

Every 8 weeks

Results posted on

2016-04-22

Participant Flow

Patients were enrolled to the trial between December 2007 and January 2009

Participant milestones

Participant milestones
Measure	Treatment (Enzyme Inhibitor Therapy) Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Overall Study STARTED	29
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Enzyme Inhibitor Therapy) Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Overall Study ineligible, incorrect diagnosis	1

Baseline Characteristics

Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Age, Continuous	55.6 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	28 patients n=5 Participants
Eastern Cooperative Oncology Group (ECOG) 0 (Fully active)	11 patients n=5 Participants
Eastern Cooperative Oncology Group (ECOG) 1 (Restricted activity)	17 patients n=5 Participants
Disease site Intrahepatic	17 patients n=5 Participants
Disease site Gallbladder	7 patients n=5 Participants
Disease site Extrahepatic	4 patients n=5 Participants
Metastasis site Liver only	7 patients n=5 Participants
Metastasis site Liver and other sites	16 patients n=5 Participants
Metastasis site Other (soft tissue, lymph nodes and lung)	5 patients n=5 Participants
Number of target lesions	4 lesions n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=25 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Objective Response Rate (CR and PR) Complete Response	0 patients
Objective Response Rate (CR and PR) Partial Response	3 patients

SECONDARY outcome

Timeframe: From the time of first treatment with AZD6244, assessed up to 4 weeks

Toxicitity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Toxicity Profile of AZD6244 Rash	90 percent of patients
Toxicity Profile of AZD6244 Xerostomia	54 percent of patients
Toxicity Profile of AZD6244 Nausea	50 percent of patients

SECONDARY outcome

Timeframe: Up to 6 months

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Median Progression Free Survival for Patients	3.7 months Interval 3.5 to 4.9

SECONDARY outcome

Timeframe: Up to 12 months

Population: Kaplan-Meier

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Overall Survival	9.8 months Interval 3.5 to Too early to reach the upper 95% confidence interval

SECONDARY outcome

Timeframe: At baseline

Population: Data was not collected and analyzed

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline

Population: Only 27 patients had pAKT and pERK performed due to 2 samples not available for analysis

Measure the proteins levels of RAS/RAF/MEK/ERK signaling pathway activation to AZD6244

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 Participants Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation pERK	1.36 mg/ml Standard Deviation 1.09
Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation pAKT	1.23 mg/ml Standard Deviation 0.98

Adverse Events

Treatment (Enzyme Inhibitor Therapy)

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Enzyme Inhibitor Therapy) n=28 participants at risk Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. selumetinib: Given orally laboratory biomarker analysis: Correlative studies
Skin and subcutaneous tissue disorders Rash	89.3% 25/28 • Number of events 25 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Xerostomia	53.6% 15/28 • Number of events 15 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Nausea	50.0% 14/28 • Number of events 14 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Vomiting	50.0% 14/28 • Number of events 14 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Diarrhea	46.4% 13/28 • Number of events 13 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Bloating	42.9% 12/28 • Number of events 12 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Skin and subcutaneous tissue disorders Dry Skin	39.3% 11/28 • Number of events 11 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Nervous system disorders Dysgeusia	28.6% 8/28 • Number of events 8 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Mucositis	25.0% 7/28 • Number of events 7 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Gastrointestinal disorders Flatulence	21.4% 6/28 • Number of events 6 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Injury, poisoning and procedural complications Thrombocytopenia	10.7% 3/28 • Number of events 3 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Skin and subcutaneous tissue disorders Pruritus	14.3% 4/28 • Number of events 4 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Skin and subcutaneous tissue disorders Alopecia	10.7% 3/28 • Number of events 3 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.
Metabolism and nutrition disorders Hypokalemia	10.7% 3/28 • Number of events 3 • All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.

Additional Information

Tanios Bekaii-Saab, MD

The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute

Phone: 614-293-9863

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60