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

January 13, 2016 updated by: AstraZeneca

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
172

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Manchester, United Kingdom
        • Research Site
      • Sutton, United Kingdom
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 150 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to 21 days from first multiple dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Best Objective Response
Time Frame: Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
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
Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
Maximum Concentration (Cmax) Single Dose
Time Frame: Following Single Dose up to 12, 24 or 48 hours post dose
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)
Following Single Dose up to 12, 24 or 48 hours post dose
Area Under the Curve (AUC) Single Dose
Time Frame: Following Single Dose up to 12, 24 or 48 hours post dose
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)
Following Single Dose up to 12, 24 or 48 hours post dose
Maximum Concentration (Cmax) at Steady State
Time Frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
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)
Multiple dosing to steady state (up to 12 or 48 hours post dose)
Area Under the Curve (AUC) at Steady State
Time Frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
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)
Multiple dosing to steady state (up to 12 or 48 hours post dose)
Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose
Time Frame: Pre dose through to 12 hours post dose
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)
Pre dose through to 12 hours post dose
Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State
Time Frame: Pre dose through to 24 hours post dose
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)
Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) Single Dose
Time Frame: Pre dose through to 24 hours post dose
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)
Pre dose through to 24 hours post dose
Urine PK - Renal Clearance (Renal CL) at Steady State
Time Frame: Pre dose through to 24 hours post dose
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)
Pre dose through to 24 hours post dose
Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose
Time Frame: predose and 2 hours after a single dose
Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)
predose and 2 hours after a single dose
Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose
Time Frame: predose and 2 hours after a single dose
Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)
predose and 2 hours after a single dose
Partial Metabolic Response (PMR), Cycle 1
Time Frame: Cycle 1 Day 8
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)
Cycle 1 Day 8
Partial Metabolic Response (PMR), Cycle 2
Time Frame: Cycle 2 Day 8
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)
Cycle 2 Day 8
Complete Metabolic Response (CMR), Cycle 1
Time Frame: Cycle 1 Day 8
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)
Cycle 1 Day 8
Complete Metabolic Response (CMR), Cycle 2
Time Frame: Cycle 2 Day 8
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)
Cycle 2 Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dr. Udai Banerji, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT
  • Study Director: Elisabeth Oelmann, AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 3, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 11, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D2270C00001
  • 2009-015244-42 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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