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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.

AZD2014

Dr. Udai Banerji

Elisabeth Oelmann

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 to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014

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

Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in \>1 patient

Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm

Maximum concentration following single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Area under the curve following single dose Continuous dosing - AUC parameter used Intermittent dosing - AUC(0-12) used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Cmax at steady state (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

AUC at steady state Continuous dosing - AUCss used Intermittent dosing - Weekly AUC used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Fraction dose excreted unchanged in the urine from 0-12 hours after a single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Fraction dose excreted unchanged in the urine from 0-12 hours after dosing (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)

Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)

Partial metabolic responses measured by 2-\[F-18\]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Complete metabolic responses measured by 2-\[F-18\]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

AstraZeneca

Continuous BD solution dosing cohorts 25mg, 50mg, 70mg, 100mg Continuous BD tablet dosing cohort Fed/Fasted 50mg Continuous QD solution dosing cohorts 75mg, 125mg Continuous Qd tablet dosing cohorts 100mg, 125mg, 175mg Intermmittent BD tablet dosing cohorts 100mg, 125mg, 170mg, 225mg

Part A - AZD2014 100 mg BD Solution

Part A - AZD2014 100 mg QD Tablet

Part A - AZD2014 125 mg QD Solution

Part A - AZD2014 125 mg QD Tablet

Part A - AZD2014 175 mg QD Tablet

Part A - AZD2014 25 mg BD Solution

Part A - AZD2014 50 mg BD Solution

Part A - AZD2014 70 mg BD Solution

Part A - AZD2014 75 mg QD Solution

Part A - Intermittent AZD2014 100 mg BD Tablet

Part A - Intermittent AZD2014 125 mg BD Tablet

Part A - Intermittent AZD2014 170 mg BD Tablet

Part A - Intermittent AZD2014 225 mg BD Tablet

Part B - AZD2014 50 mg BD Solution

Part B - AZD2014 50 mg BD Tablet Fasted/Fed

Part B - AZD2014 BD 50 mg Tablet Fed/Fasted

Part B - Intermittent AZD2014 125 mg BD Tablet

Part B - Intermittent AZD2014 170 mg BD Tablet

Part A 25mg BD Soln Cont

Part A 50mg BD Soln Cont

Part B 50mg BD Soln Cont

Part B Fed/Fasted 50mg BD Tab Cont

Part A 75mg QD Soln Cont

Part A 125mg QD Soln Cont

Part A 100mg QD Tab Cont

Part A 125mg QD Tab Cont

Part A 175mg QD Tab Cont

Part A 100mg BD Tab Int

Part A 125mg BD Tab Int

Part A 170mg BD Tab Int

Part A 225mg BD Tab Int

Part B 125mg BD Tab Int

Part B 170mg BD Tab Int

Part A 70mg BD Soln Cont

Part A 100mg BD Soln Cont

Total

Age, Continuous

Sex: Female, Male

Safety Analysis Set - All patients that received at least 1 dose of AZD2014. This includes dosed patients who are not evaluable for dose escalation decision purposes.

Bryony Harrop

Number of Participants With Dose Limiting Toxicities (DLTs)

Responders

Non-responders

Stable disease ≥8 wks (a subset of non-responders)

Efficacy analysis set - Patients who received at least 1 dose of AZD2014 and have a baseline tumour assessment

Best Objective Response

Part B 50mg BD Tablet Fasted

Part B 50mg BD Tablet Fed

Maximum Concentration (Cmax) Single Dose

Area Under the Curve (AUC) Single Dose

Maximum Concentration (Cmax) at Steady State

Area Under the Curve (AUC) at Steady State

PK analysis set - A subset of Safety Analysis set who have reportable plasma concentrations and PK parameter data and who have no important protocol deviations/AEs that may impact PK

Spots Global Cancer Trial Database for Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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