Trial Outcomes & Findings for The Biological Activity of Cediranib (AZD2171) in Gastro-Intestinal Stromal Tumours(GIST). (NCT NCT00385203)

Last Updated: 2012-07-16

Results Overview

\[F 18\] Fluoro 2 Deoxy D Glucose - Positron Emission Tomography (FDG-PET). Tumour metabolic activity as assessed by Change in Standardised Uptake Value (SUVMax) at Day 8 (measured by central review), in Patients with GIST tumours. SUVmax at Day 8 minus SUVmax at Baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Baseline and 8 days after dosing.

Results posted on

2012-07-16

Participant Flow

Enrolled: 45mg GIST=26, 45mg STS=10; Full analysis set: 45mg GIST=25, 45mg STS=10; Safety set: 45mg GIST=24, 45mg STS=10. 36 patients were enrolled and 35 patients were randomized. One GIST patient consented but had an adverse event and was withdrawn from the study before they were randomised.

Participant milestones

Participant milestones
Measure	Cediranib 45 mg/Day GIST 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS 10 Soft Tissue Sarcomas (STS) patients were randomised.
Overall Study STARTED	26	10
Overall Study COMPLETED	0	3
Overall Study NOT COMPLETED	26	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Cediranib 45 mg/Day GIST 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS 10 Soft Tissue Sarcomas (STS) patients were randomised.
Overall Study Adverse Event	5	4
Overall Study Death	1	0
Overall Study Condition under investigation worsened	18	3
Overall Study Incorrect enrollment	2	0

Baseline Characteristics

The Biological Activity of Cediranib (AZD2171) in Gastro-Intestinal Stromal Tumours(GIST).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cediranib 45 mg/Day GIST n=25 Participants Cediranib 45 mg/Day: 25 patients with Gastrointestinal Stromal Tumour (GIST) randomised	Cediranib 45 mg/Day STS n=10 Participants Cediranib 45 mg/Day: 10 patients with Soft Tissue Sarcomas (STS) randomised	Total n=35 Participants Total of all reporting groups
Age Continuous	56.1 years STANDARD_DEVIATION 9.8 • n=93 Participants	44.6 years STANDARD_DEVIATION 9.4 • n=4 Participants	52.8 years STANDARD_DEVIATION 10.9 • n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	6 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	4 Participants n=4 Participants	21 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and 8 days after dosing.

Population: As per the protocol the analysis was for GIST patients only (not STS patients). For patients to be included in the analysis they had to have scans with readable results at both timepoints (baseline and Day 8).

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=22 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Change in Standardised Uptake Value (SUV)Max at Day 8, Central Review, (GIST) Gastrointestinal Stromal Tumours Patients.	-0.515 g/mL Interval -1.48 to 0.45	—

PRIMARY outcome

Timeframe: FDG-PET assessment at Baseline and 29 days after dosing.

SUVmax at Day 29 minus SUVmax at baseline, based on central review, GIST patients

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=20 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Tumour Metabolic Activity as Assessed by Change in Central Review of Standardised Uptake Value (SUVMax) at Day 29, in Patients With GIST Tumours. SUVmax at Day 29 Minus SUVmax at Baseline.	-0.172 g/mL Interval -1.38 to 1.04	—

SECONDARY outcome

Timeframe: RECIST at Baseline, Weeks 8, 16 and every 12 weeks thereafter until progression.

Number of patients with complete (CR) /partial response (PR) (based on RECIST) as assessed by the Investigator. CR is defined as Disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of Longest Diameter (LD) of target lesions taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=24 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS n=10 Participants Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Objective Tumour Response, Investigator Review	0 Participants	4 Participants

SECONDARY outcome

Timeframe: CT assessments at Baseline and Week 8

Population: As per the protocol the formal statistical analysis was performed for the GIST grouppatients only, STS patients were summarised (not STS patients). For patients to be included in the analysis they had to have CT scans at both timepoints (baseline and week 8).

Central review of CT images taking the longest diameter measured in millimetres at week 8 \[major axis (axial plane)\] minus the longest diameter measured in millimetres at baseline.

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=18 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS n=8 Participants Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
-Tumour Activity as Measured by Major Axis (Axial Plane) at Week 8 in GIST/STS Patients by Central Review of CT Images.	2.734 mm Interval -1.76 to 7.23	-1.015 mm Interval -7.22 to 5.19

SECONDARY outcome

Timeframe: CT assessments at Baseline and Week 16.

Population: As per the protocol formal statistical analysis was performed for the GIST group only, STS patients were summarised. For patients to be included in the analysis they had to have CT scans at both timepoints (baseline and week 8).

Central review of CT images taking the longest diameter measured in millimetres at week 16 \[major axis (axial plane)\] minus the longest diameter measured in millimetres at baseline.

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=13 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS n=5 Participants Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Anti-tumour Activity as Measured by Major Axis (Axial Plane) at Week 16 in GIST/STS Patients by Central Review of CT Images.	5.028 mm Interval -1.12 to 11.18	-8.114 mm Interval -15.74 to -0.49

SECONDARY outcome

Timeframe: CT assessments at Baseline and Week 8

Central review of CT images taking the total lesion volume at week 8 minus the total lesion volume at baseline.

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=18 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS n=8 Participants Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Tumour Activity as Measured by Total Lesion Volume at Week 8 in GIST Patients by Central Review of CT Images.	19889.31 cm3 Interval -7054.96 to 46833.58	5106.30 cm3 Interval -21840.1 to 32052.7

SECONDARY outcome

Timeframe: CT assessments at Baseline and Week 16

Central review of CT images taking the total lesion volume at week 16 minus the total lesion volume at baseline.

Outcome measures

Outcome measures
Measure	Cediranib 45 mg/Day GIST n=13 Participants 26 Gastrointestinal Stromal tumour patients (GIST) were enrolled (informed consent received), one patient was enrolled but had an AE prior to randomisation so were withdrawn from the study. No demographic data were obtained for this patient.	Cediranib 45 mg/Day STS n=5 Participants Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment
Anti-tumour Activity as Measured by Total Lesion Volume at Week 16 in GIST Patients by Central Review of CT Images.	43202.54 cm3 Interval -4505.18 to 90910.27	-6479.65 cm3 Interval -15411.92 to 2452.63

Adverse Events

Cediranib 45 mg/Day GIST

Serious events: 10 serious events

Other events: 24 other events

Deaths: 0 deaths

Cediranib 45 mg/Day STS

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cediranib 45 mg/Day GIST n=24 participants at risk Cediranib 45 mg/Day patients with Gastrointestinal Stromal Tumour (GIST): 24 patients randomised and received at least one dose of treatment (1 patient was not randomised or dosed and a further 1 patient was randomised but not dosed due to Incorrect enrolmentCediranib)	Cediranib 45 mg/Day STS n=10 participants at risk Cediranib 45 mg/Day patients with Soft Tissue Sarcomas (STS): 10 patients randomised and received at least one dose of treatment.
Vascular disorders Anaemia	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Abdominal Discomfort	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Abdominal Pain	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	10.0% 1/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Constipation	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Diarrhoea	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Intestinal Obstruction	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Gastrointestinal disorders Vomiting	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
General disorders Fatigue	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
General disorders Non-Cardiac Chest Pain	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Hepatobiliary disorders Hepatic Haemorrhage	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Hepatobiliary disorders Jaundice	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Nervous system disorders Cerebrovascular Accident	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Nervous system disorders Convulsion	0.00% 0/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	10.0% 1/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Psychiatric disorders Psychotic Disorder	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Renal and urinary disorders Renal Impairment	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Vascular disorders Hypertension	0.00% 0/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	10.0% 1/10 Adverse events are reported for randomised patients who received at least one dose of treatment.
Vascular disorders Hypertensive Crisis	4.2% 1/24 Adverse events are reported for randomised patients who received at least one dose of treatment.	0.00% 0/10 Adverse events are reported for randomised patients who received at least one dose of treatment.