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OpenTrials
Completed

NCT Number: NCT01026402

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

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.

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Key information

Conditions

Advanced Solid Malignancies Neoplasms

Age range

18 year–150 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Manchester, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AZD2014

Drug

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.

Primary outcomes

  1. 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

  1. 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

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2014
Study completion
2014
First posted
Dec 4, 2009
Registry last updated
Feb 11, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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