Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Advanced Solid Malignancies	Drug: AZD2014	Phase 1

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Safety and tolerability of AZD2014 [ Time Frame: Assessed at all visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	115
Study Start Date:	December 2009
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AZD2014 AZD2014 dose escalation phase in Part A and expansion phase in Part B.	Drug: AZD2014 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.

Arms

Assigned Interventions

Experimental: AZD2014

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

Drug: AZD2014

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 from 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026402

Contacts

Contact: AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Locations

United Kingdom
Research Site	Recruiting
Sutton, Surrey, United Kingdom
Research Site	Recruiting
Manchester, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator:	Dr. Udai Banerji	The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT
Study Director:	Louise Grochow, Dr	AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01026402 History of Changes
Other Study ID Numbers:	D2270C00001, EudraCT number: 2009-015244-42
Study First Received:	December 3, 2009
Last Updated:	April 30, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Phase I
cancer
advanced solid malignancies
dose escalation

AZD2014
mTor kinase inhibitor
safety
pharmacokinetics

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on June 17, 2013