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:||February 2014|
|Estimated Primary Completion Date:||February 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.
|Contact: AstraZeneca Clinical Study Informationemail@example.com|
|Sutton, Surrey, United Kingdom|
|Manchester, United Kingdom|
|Principal Investigator:||Dr. Udai Banerji||The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT|
|Study Director:||Elisabeth Oelmann||AstraZeneca|