Cancer
Conditions
Keywords
Advanced solid tumours, Advanced cancer, tumor, tumour, RECENTIN
Brief summary
The purpose of this study is to determine whether food has any effect on a single dose of Cediranib (AZD2171, Recentin™)followed by an assessment of the safety and tolerability of fixed daily dosing in comparison to varying dose levels on a patient-by-patient basis.
Interventions
DRUGCediranib
45 mg oral dose
DRUGCediranib 30 - 90 mg
oral tablet dose escalation
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of advanced solid tumour. * Ability to eat a high fat breakfast
Exclusion criteria
* Poorly controlled high blood pressure. * History of significant gastrointestinal problems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Area Under Plasma Concentration-time Curve (AUC) | Measurements were collected up to 168 hours (following single dosing). | Area under plasma concentration-time curve from zero to infinity |
| Part A: Maximum Plasma (Peak) Concentration (Cmax) | Measurements were collected up to 168 hours (following single dosing). | Maximum plasma drug concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Terminal Phase Half-life (t1/2λz) | Measurements were collected up to 168 hours (following single dosing). | Terminal phase half-life |
| Part A: Apparent Total Body Clearance (CL/F) | Measurements were collected up to 168 hours (following single dosing). | Apparent total body clearance of drug from plasma |
| Part A: AUC (0-t) | Measurements were collected up to 168 hours (following single dosing). | Area under the curve from time 0 to the last measureable time point |
| Part B: Progression-free Survival (PFS) | Number of days from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression. | Target lesions: Progressive Disease (PD) At least a 20% increase in the sum of LD (longest diameter)of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began). Non target lesions: Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing non-target lesions. |
| Part B: Best Overall Response Rate (ORR) | Baseline, week 8, week 16 and every 8 weeks thereafter until discontinuation. | Evaluation of target lesions Complete Response(CR)Disappearance of all target lesions Partial Response(PR) At least a 30% decrease in the sum of LD(longest diameter)of target lesions taking as reference the baseline sum LD.Progressive Disease(PD).At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded(either at baseline or at previous assessment since treatment began).Stable Disease(SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Note: Appearance of new lesions only counts towards the overall visit response,not towards the response of target or non-target lesions. Evaluation of non-target lesions Complete Response(CR)Disappearance of all non-target lesions Non-Complete Response(non-CR/Non-Progression\[non-PD\])Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits.Progression(PD)Unequivocal progression of existing non-target lesions |
| Part A: Time to Peak or Maximum Concentration (Tmax) | Measurements were collected up to 168 hours (following single dosing). | Time to reach peak or maximum concentration or maximum response |
Countries
United Kingdom
Participant flow
Recruitment details
This was a two part study.Part A had two arms, fed/fasted and fasted/fed. Part B had two arms, a fixed dose arm and a dose escalation arm.Patients(pts)in Part A were allowed to go in to Part B. Pts who chose not to go in to Part B discontinued the study.Additionally new pts were recruited to Part B. In Parts A/B, there was a total of 60 pts.
Pre-assignment details
60 patients were enrolled though only 45 patients were randomized to Part A and 47 to Part B. Completion of Part B means completed at least 16 weeks of treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cediranib 45 mg Fed Part A: Cediranib 45 mg Fed State | 23 |
| Cediranib 45 mg Fasted Part A: Cediranib 45 mg Fasted State | 22 |
| Cediranib 45 mg Fixed Dose Part B: Cediranib 45 mg Fixed Dose | 16 |
| Cediranib 30 to 90 mg Dose Escalation Part B: Cediranib Dose Escalation | 31 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part A | Condition under investigation worsened | 2 | 2 | 0 | 0 |
| Part A | Incorrect enrol/entry crit not fulfilled | 0 | 1 | 0 | 0 |
| Part A | Partial bowel obstruction | 1 | 0 | 0 | 0 |
| Part A | QTC interval outwith elig. criteria | 1 | 0 | 0 | 0 |
| Part A | Reaccumul. of ascites following drainage | 0 | 1 | 0 | 0 |
| Part A | Suspicion of second malignancy | 0 | 1 | 0 | 0 |
| Part A | Withdrawal by Subject | 1 | 1 | 0 | 0 |
| Part B | Adverse Event | 0 | 0 | 5 | 5 |
| Part B | Condition under investigation worsened | 0 | 0 | 2 | 8 |
| Part B | Death | 0 | 0 | 1 | 2 |
| Part B | Development of study specific disc crit. | 0 | 0 | 0 | 1 |
| Part B | Withdrawal by Subject | 0 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Cediranib 30 to 90 mg Dose Escalation | Cediranib 45 mg Fasted | Cediranib 45 mg Fed | Cediranib 45 mg Fixed Dose |
|---|---|---|---|---|---|
| Age Continuous | 56.0 Years STANDARD_DEVIATION 13 | 56.0 Years STANDARD_DEVIATION 13.5 | 51.2 Years STANDARD_DEVIATION 14.8 | 58.6 Years STANDARD_DEVIATION 10.6 | 56.4 Years STANDARD_DEVIATION 13.1 |
| Sex/Gender, Customized Female, Part A | 20 participants | NA participants | 10 participants | 10 participants | NA participants |
| Sex/Gender, Customized Female, Part B | 20 participants | 12 participants | NA participants | NA participants | 8 participants |
| Sex/Gender, Customized Male, Part A | 25 participants | NA participants | 12 participants | 13 participants | NA participants |
| Sex/Gender, Customized Male, Part B | 27 participants | 19 participants | NA participants | NA participants | 8 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 39 | 16 / 16 | 31 / 31 |
| serious Total, serious adverse events | 6 / 39 | 9 / 16 | 20 / 31 |
Outcome results
Primary
Part A: Area Under Plasma Concentration-time Curve (AUC)
Area under plasma concentration-time curve from zero to infinity
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: Area Under Plasma Concentration-time Curve (AUC) | 1920 ng*h/mL |
| Cediranib 45 mg Fasted | Part A: Area Under Plasma Concentration-time Curve (AUC) | 2392 ng*h/mL |
Primary
Part A: Maximum Plasma (Peak) Concentration (Cmax)
Maximum plasma drug concentration
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: Maximum Plasma (Peak) Concentration (Cmax) | 87.02 ng/mL |
| Cediranib 45 mg Fasted | Part A: Maximum Plasma (Peak) Concentration (Cmax) | 127.9 ng/mL |
Secondary
Part A: Apparent Total Body Clearance (CL/F)
Apparent total body clearance of drug from plasma
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: Apparent Total Body Clearance (CL/F) | 23.44 L/h |
| Cediranib 45 mg Fasted | Part A: Apparent Total Body Clearance (CL/F) | 18.81 L/h |
Secondary
Part A: AUC (0-t)
Area under the curve from time 0 to the last measureable time point
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: AUC (0-t) | 1896 ng*h/mL |
| Cediranib 45 mg Fasted | Part A: AUC (0-t) | 2348 ng*h/mL |
Secondary
Part A: Terminal Phase Half-life (t1/2λz)
Terminal phase half-life
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: Terminal Phase Half-life (t1/2λz) | 23.99 hr |
| Cediranib 45 mg Fasted | Part A: Terminal Phase Half-life (t1/2λz) | 24.72 hr |
Secondary
Part A: Time to Peak or Maximum Concentration (Tmax)
Time to reach peak or maximum concentration or maximum response
Time frame: Measurements were collected up to 168 hours (following single dosing).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part A: Time to Peak or Maximum Concentration (Tmax) | 4.59 hr |
| Cediranib 45 mg Fasted | Part A: Time to Peak or Maximum Concentration (Tmax) | 3.52 hr |
Secondary
Part B: Best Overall Response Rate (ORR)
Evaluation of target lesions Complete Response(CR)Disappearance of all target lesions Partial Response(PR) At least a 30% decrease in the sum of LD(longest diameter)of target lesions taking as reference the baseline sum LD.Progressive Disease(PD).At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded(either at baseline or at previous assessment since treatment began).Stable Disease(SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Note: Appearance of new lesions only counts towards the overall visit response,not towards the response of target or non-target lesions. Evaluation of non-target lesions Complete Response(CR)Disappearance of all non-target lesions Non-Complete Response(non-CR/Non-Progression\[non-PD\])Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits.Progression(PD)Unequivocal progression of existing non-target lesions
Time frame: Baseline, week 8, week 16 and every 8 weeks thereafter until discontinuation.
Population: ITT (intention-to-treat ) patients with baseline RECIST data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cediranib 45 mg Fed | Part B: Best Overall Response Rate (ORR) | 1 Participants |
| Cediranib 45 mg Fasted | Part B: Best Overall Response Rate (ORR) | 3 Participants |
Secondary
Part B: Progression-free Survival (PFS)
Target lesions: Progressive Disease (PD) At least a 20% increase in the sum of LD (longest diameter)of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began). Non target lesions: Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing non-target lesions.
Time frame: Number of days from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.
Population: ITT (intention-to-treat ) patients with baseline RECIST data.One patient was randomized and had baseline RECIST assessments, but did not have any further RECIST assessments. Therefore they were censored at baseline, meaning the lowest value in the range was set to zero.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cediranib 45 mg Fed | Part B: Progression-free Survival (PFS) | 135 Days |
| Cediranib 45 mg Fasted | Part B: Progression-free Survival (PFS) | 139 Days |