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

AstraZeneca1 site in 1 country172 target enrollmentDecember 2009

ConditionsAdvanced Solid Malignancies

InterventionsAZD2014

DrugsAZD2014

Overview

Phase: Phase 1
Intervention: AZD2014
Conditions: Advanced Solid Malignancies
Sponsor: AstraZeneca
Enrollment: 172
Locations: 1
Primary Endpoint: Number of Participants With Dose Limiting Toxicities (DLTs)
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

December 2009

End Date

August 2014

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist
•At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
•World Health Organisation performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks

Exclusion Criteria

•Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks prior to first dose of study drug
•Patients with abnormal fasting glucose, type I or uncontrolled type II diabetes
•Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions

Arms & Interventions

AZD2014

AZD2014 dose escalation phase in Part A and expansion phase in Part B.

Intervention: AZD2014

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

Time Frame: Up to 21 days from first multiple dose

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

Secondary Outcomes

Maximum Concentration (Cmax) Single Dose(Following Single Dose up to 12, 24 or 48 hours post dose)
Partial Metabolic Response (PMR), Cycle 1(Cycle 1 Day 8)
Area Under the Curve (AUC) Single Dose(Following Single Dose up to 12, 24 or 48 hours post dose)
Maximum Concentration (Cmax) at Steady State(Multiple dosing to steady state (up to 12 or 48 hours post dose))
Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State(Pre dose through to 24 hours post dose)
Urine PK - Renal Clearance (Renal CL) at Steady State(Pre dose through to 24 hours post dose)
Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose(predose and 2 hours after a single dose)
Complete Metabolic Response (CMR), Cycle 1(Cycle 1 Day 8)
Complete Metabolic Response (CMR), Cycle 2(Cycle 2 Day 8)
Best Objective Response(Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months)
Partial Metabolic Response (PMR), Cycle 2(Cycle 2 Day 8)
Area Under the Curve (AUC) at Steady State(Multiple dosing to steady state (up to 12 or 48 hours post dose))
Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose(Pre dose through to 12 hours post dose)
Urine PK - Renal Clearance (Renal CL) Single Dose(Pre dose through to 24 hours post dose)
Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose(predose and 2 hours after a single dose)