Effect of Food Upon Pharmacokinetics of Single Oral Dose of Cediranib (AZD2171, Recentin™)

Study Overview
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Brief Summary
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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.

Official Title
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Open-label, Randomised, Phase 2 Study in Patients With Advanced Solid Tumours to Determine Effect of Food Upon Pharmacokinetics of a Single Oral Dose of Cediranib (AZD2171, Recentin™), Followed by an Assessment of the Safety & Tolerability of Fixed and Individualised Daily Dosing

Conditions
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Cancer

Intervention / Treatment
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* Drug: Cediranib
* Drug: Cediranib 30 - 90 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cediranib 45 mg Fed<br>Part A: Cediranib 45 mg Fed State | Drug: Cediranib<br>* 45 mg oral dose<br>* Other names: RECENTIN™;|
| Experimental: Cediranib 45 mg Fasted<br>Part A: Cediranib 45 mg Fasted State | Drug: Cediranib<br>* 45 mg oral dose<br>* Other names: RECENTIN™;|
| Experimental: Cediranib 45 mg Fixed Dose<br>Part B: Cediranib 45 mg Fixed Dose | Drug: Cediranib<br>* 45 mg oral dose<br>* Other names: RECENTIN™;|
| Experimental: Cediranib 30 - 90 mg Dose Escalation<br>Part B: Cediranib 30 - 90 mg Dose Escalation | Drug: Cediranib 30 - 90 mg<br>* oral tablet dose escalation<br>* Other names: RECENTIN™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Area Under Plasma Concentration-time Curve (AUC) | Area under plasma concentration-time curve from zero to infinity | Measurements were collected up to 168 hours (following single dosing). | 
| Part A: Maximum Plasma (Peak) Concentration (Cmax) | Maximum plasma drug concentration | Measurements were collected up to 168 hours (following single dosing). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: AUC (0-t) | Area under the curve from time 0 to the last measureable time point | Measurements were collected up to 168 hours (following single dosing). | 
| Part A: Time to Peak or Maximum Concentration (Tmax) | Time to reach peak or maximum concentration or maximum response | Measurements were collected up to 168 hours (following single dosing). | 
| Part A: Terminal Phase Half-life (t1/2λz) | Terminal phase half-life | Measurements were collected up to 168 hours (following single dosing). | 
| Part A: Apparent Total Body Clearance (CL/F) | Apparent total body clearance of drug from plasma | Measurements were collected up to 168 hours (following single dosing). | 
| 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 | Baseline, week 8, week 16 and every 8 weeks thereafter until discontinuation. | 
| 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumours, Advanced cancer, tumor, tumour, RECENTIN