Trial Outcomes & Findings for Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer (NCT NCT00604721)

Last Updated: 2014-05-28

Results Overview

To ascertain the objective response rate (Complete Response + Partial Response \[CR+PR\]) of patients with the single-agent AZD6244. Our study utilized Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

33 weeks

Results posted on

2014-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	AZD6244 Treatment The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was to be determined by the algorithm presented in the safety cohort.
Overall Study STARTED	19
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD6244 Treatment The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was to be determined by the algorithm presented in the safety cohort.
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD6244 Treatment n=19 Participants The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was to be determined by the algorithm presented in the safety cohort.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=99 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants
Age, Customized	57 years n=99 Participants
Sex: Female, Male Female	6 Participants n=99 Participants
Sex: Female, Male Male	13 Participants n=99 Participants
Region of Enrollment United States	19 participants n=99 Participants

PRIMARY outcome

Timeframe: 33 weeks

Population: Participants who completed a full 21 day cycle of therapy

Outcome measures

Outcome measures
Measure	Safety Cohort: AZD6244 Treatment n=17 Participants The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was determined by the algorithm presented in the safety cohort.
Number of Participants With Radiographic Objective Response (OR)	0 participants

SECONDARY outcome

Timeframe: 33 weeks

Population: Participants who completed a full 21 day cycle of therapy

Progression free survival has been defined as time from the start of treatment to disease progression or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Safety Cohort: AZD6244 Treatment n=17 Participants The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was determined by the algorithm presented in the safety cohort.
Median Progression Free Survival (PFS)	1.4 months Interval 1.2 to 2.5

SECONDARY outcome

Timeframe: 33 weeks

Population: Participants who completed a full 21 day cycle of therapy

Overall survival has been defined as time from the start of treatment to death as a result of any cause.

Outcome measures

Outcome measures
Measure	Safety Cohort: AZD6244 Treatment n=17 Participants The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was determined by the algorithm presented in the safety cohort.
Median Overall Survival (OS)	4.2 months Interval 1.9 to 6.0

Adverse Events

AZD6244 Treatment

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD6244 Treatment n=19 participants at risk The first 6 patients with moderate liver dysfunction (Child's B or total bilirubin 1.5-2x ULN) were to comprise a "moderate liver dysfunction" safety cohort. AZD6244 was administered at a dose of 100 mg twice daily (48 hours after initial single dose for PK), approximately 12 hours apart, in a mix and drink formulation. For the purposes of evaluation, a cycle was defined as 21 days. Dosing for the remainder of patients (efficacy cohort) was to be determined by the algorithm presented in the safety cohort.
General disorders Death - Death not associated with CTCAE term - Disease progression - 1 Event definitely related	26.3% 5/19 • Number of events 5 • 1 year, 5 months All 19 participants were evaluated for toxicity.
General disorders Hemorrhage/Bleeding - GI - Liver - Unrelated	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Hepatobiliary disorders Hepatobiliary/Pancreas - Liver dysfunction/failure - Unrelated	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Gastrointestinal disorders Gastrointestinal - Other - Unlikely to be related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Metabolism and nutrition disorders AST, SGOT - Probably related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Metabolism and nutrition disorders AST, SGOT - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Gastrointestinal disorders Nausea - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Blood and lymphatic system disorders Hemoglobin - Possbily related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Blood and lymphatic system disorders Hemoglobin - Unlikely to be related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Metabolism and nutrition disorders Bilirubin - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
General disorders Hemorrhage/Bleeding - GU/Urinary - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
General disorders Fatigue - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia) - Possibly related	5.3% 1/19 • Number of events 1 • 1 year, 5 months All 19 participants were evaluated for toxicity.

Other adverse events

Adverse event data not reported

Additional Information

Bert. H. O'Neil, Associate Professor, Clinical Research

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-4431

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60