Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014
The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. The study will also assess the blood levels and action of AZD2014 in the body over a period of time and will indicate whether the drug has an effect on the types of cancer the patients have.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTor Kinase Inhibitor AZD2014 Administered Orally to Patients With Advanced Solid Malignancies|
- Safety and tolerability of AZD2014 [ Time Frame: Assessed at all visits ] [ Designated as safety issue: Yes ]
- Evaluate the pharmacokinetics of AZD2014 following both single and multiple dosing [ Time Frame: Part A: Cycle 1 single dose days 1 -3; multiple dose days 8, 15 & 21; Intermittent schedules, Cycle 1 Days 1-3 & 7-11 ] [ Designated as safety issue: Yes ]
- Obtain a preliminary assessment of the anti-tumour activity of AZD2014 by evaluation of tumour response using modified RECIST version 1.1. and to determine inhibition of tumour glucose uptake by assessment with FDG-PET. [ Time Frame: RECIST assessments (CT/MRI/clinical examination) in parts A and B taken at baseline and then every 8 weeks after start of treatment. FDG-PET assessments taken in parts A and B,at screening, cycle 1 multiple dose day 8 and cycle 2 multiple dose day 8. ] [ Designated as safety issue: No ]
- Evaluate the levels of phosphorylation of pharmacodynamic biomarkers (following treatment with AZD2014) and to investigate possible relationships between plasma AZD2014 concentrations/exposure and changes in safety and biomarkers [ Time Frame: PD blood sampling, Part A: Screening, Cycle 1 Single dose Days 1-3 ; Multi dose Day 21; Intermittent schedules, Cycle 1 Days 1-3 & 7-11. Part B: - Screening, Cycle 1 Day 1, 2, 3, 21 & 28.Intermittent schedules, Cycle 1 Days 1-3 & 7-11. ] [ Designated as safety issue: Yes ]
- To determine the role of renal excretion in the clearance of AZD2014. [ Time Frame: PK sample timings as detailed above ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
AZD2014 dose escalation phase in Part A and expansion phase in Part B.
Dose escalation phase: a single dose taken orally (solution or tablet) of AZD2014 on single dose day 1 (visit 2), followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or Single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. Expansion phase: twice daily dosing from day 1 until discontinuation or withdrawal or a single dose taken orally of AZD2014 on single dose day 1 (visit 2), followed by a single dose on second single dose day 1 (visit 3) after a washout period (48 hours - 7 days) followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01026402
|Manchester, United Kingdom|
|Sutton, United Kingdom|
|Principal Investigator:||Dr. Udai Banerji||The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT|
|Study Director:||Elisabeth Oelmann||AstraZeneca|