Clinical trial NCT01026402: Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Malignancies
Keywords: Phase I
cancer
advanced solid malignancies
dose escalation
AZD2014
mTor kinase inhibitor
safety
pharmacokinetics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-12-04
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 21 days from first multiple dose
Secondary outcomes:
measure: Best Objective Response
timeFrame: Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
measure: Maximum Concentration (Cmax) Single Dose
timeFrame: Following Single Dose up to 12, 24 or 48 hours post dose
measure: Area Under the Curve (AUC) Single Dose
timeFrame: Following Single Dose up to 12, 24 or 48 hours post dose
measure: Maximum Concentration (Cmax) at Steady State
timeFrame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
measure: Area Under the Curve (AUC) at Steady State
timeFrame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
measure: Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose
timeFrame: Pre dose through to 12 hours post dose
measure: Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State
timeFrame: Pre dose through to 24 hours post dose
measure: Urine PK - Renal Clearance (Renal CL) Single Dose
timeFrame: Pre dose through to 24 hours post dose
measure: Urine PK - Renal Clearance (Renal CL) at Steady State
timeFrame: Pre dose through to 24 hours post dose
measure: Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose
timeFrame: predose and 2 hours after a single dose
measure: Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose
timeFrame: predose and 2 hours after a single dose
measure: Partial Metabolic Response (PMR), Cycle 1
timeFrame: Cycle 1 Day 8
measure: Partial Metabolic Response (PMR), Cycle 2
timeFrame: Cycle 2 Day 8
measure: Complete Metabolic Response (CMR), Cycle 1
timeFrame: Cycle 1 Day 8
measure: Complete Metabolic Response (CMR), Cycle 2
timeFrame: Cycle 2 Day 8
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT
name: Dr. Udai Banerji
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Elisabeth Oelmann
role: STUDY_DIRECTOR
References: