Gastrointestinal Stromal Tumors, Soft Tissue Sarcomas
Conditions
Keywords
cancer, tumour, advanced cancer, Metastatic Gastro-Intestinal Stromal Tumours, gastro-intestinal cancer, RECENTIN
Brief summary
To determine the anti-tumour activity and biological effects of cediranib (AZD2171) at a dose of 45mg, primarily in Gastrointestinal Stromal Tumour (GIST) patients who are resistant to imatinib mesylate (current standard therapy) and also in patients with metastatic Soft Tissue Sarcoma (STS) resistant to standard therapy.
Interventions
DRUGAZD2171
45 mg oral tablet once daily dose
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmation of GIST which is resistant or intolerant to imatinib mesylate, or metastatic STS, which is refractory to standard therapies or for which no standard therapy exists
Exclusion criteria
* Patients with type I insulin-dependent diabetes or poorly-controlled type II insulin-independent diabetes. * Patients with a history of poorly controlled high blood pressure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Standardised Uptake Value (SUV)Max at Day 8, Central Review, (GIST) Gastrointestinal Stromal Tumours Patients. | Baseline and 8 days after dosing. | \[F 18\] 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. |
| 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. | FDG-PET assessment at Baseline and 29 days after dosing. | SUVmax at Day 29 minus SUVmax at baseline, based on central review, GIST patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumour Activity as Measured by Major Axis (Axial Plane) at Week 16 in GIST/STS Patients by Central Review of CT Images. | CT assessments at Baseline and Week 16. | 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. |
| Objective Tumour Response, Investigator Review | 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. |
| Anti-tumour Activity as Measured by Total Lesion Volume at Week 16 in GIST Patients by Central Review of CT Images. | 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. |
| Tumour Activity as Measured by Total Lesion Volume at Week 8 in GIST Patients by Central Review of CT Images. | 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. |
| -Tumour Activity as Measured by Major Axis (Axial Plane) at Week 8 in GIST/STS Patients by Central Review of CT Images. | CT assessments at 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cediranib 45 mg/Day GIST Cediranib 45 mg/Day: 25 patients with Gastrointestinal Stromal Tumour (GIST) randomised | 25 |
| Cediranib 45 mg/Day STS Cediranib 45 mg/Day: 10 patients with Soft Tissue Sarcomas (STS) randomised | 10 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Condition under investigation worsened | 18 | 3 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Incorrect enrollment | 2 | 0 |
Baseline characteristics
| Characteristic | Cediranib 45 mg/Day GIST | Cediranib 45 mg/Day STS | Total |
|---|---|---|---|
| Age Continuous | 56.1 years STANDARD_DEVIATION 9.8 | 44.6 years STANDARD_DEVIATION 9.4 | 52.8 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 17 Participants | 4 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 10 / 10 |
| serious Total, serious adverse events | 10 / 24 | 3 / 10 |
Outcome results
Primary
Change in Standardised Uptake Value (SUV)Max at Day 8, Central Review, (GIST) Gastrointestinal Stromal Tumours Patients.
\[F 18\] 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.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | Change in Standardised Uptake Value (SUV)Max at Day 8, Central Review, (GIST) Gastrointestinal Stromal Tumours Patients. | -0.515 g/mL |
Primary
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.
SUVmax at Day 29 minus SUVmax at baseline, based on central review, GIST patients
Time frame: FDG-PET assessment at Baseline and 29 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 29).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | 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 |
Secondary
Anti-tumour Activity as Measured by Major Axis (Axial Plane) at Week 16 in GIST/STS Patients by Central Review of CT Images.
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.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | 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 |
| Cediranib 45 mg/Day STS | Anti-tumour Activity as Measured by Major Axis (Axial Plane) at Week 16 in GIST/STS Patients by Central Review of CT Images. | -8.114 mm |
Secondary
Anti-tumour Activity as Measured by Total Lesion Volume at Week 16 in GIST Patients by Central Review of CT Images.
Central review of CT images taking the total lesion volume at week 16 minus the total lesion volume at baseline.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | Anti-tumour Activity as Measured by Total Lesion Volume at Week 16 in GIST Patients by Central Review of CT Images. | 43202.54 cm3 |
| Cediranib 45 mg/Day STS | Anti-tumour Activity as Measured by Total Lesion Volume at Week 16 in GIST Patients by Central Review of CT Images. | -6479.65 cm3 |
Secondary
Objective Tumour Response, Investigator Review
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.
Time frame: RECIST at Baseline, Weeks 8, 16 and every 12 weeks thereafter until progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cediranib 45 mg/Day GIST | Objective Tumour Response, Investigator Review | 0 Participants |
| Cediranib 45 mg/Day STS | Objective Tumour Response, Investigator Review | 4 Participants |
Secondary
-Tumour Activity as Measured by Major Axis (Axial Plane) at Week 8 in GIST/STS Patients by Central Review of CT Images.
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.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | -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 |
| Cediranib 45 mg/Day STS | -Tumour Activity as Measured by Major Axis (Axial Plane) at Week 8 in GIST/STS Patients by Central Review of CT Images. | -1.015 mm |
Secondary
Tumour Activity as Measured by Total Lesion Volume at Week 8 in GIST Patients by Central Review of CT Images.
Central review of CT images taking the total lesion volume at week 8 minus the total lesion volume at baseline.
Time frame: CT assessments at Baseline and Week 8
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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cediranib 45 mg/Day GIST | Tumour Activity as Measured by Total Lesion Volume at Week 8 in GIST Patients by Central Review of CT Images. | 19889.31 cm3 |
| Cediranib 45 mg/Day STS | Tumour Activity as Measured by Total Lesion Volume at Week 8 in GIST Patients by Central Review of CT Images. | 5106.30 cm3 |