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NCT02403895

AZD2014 and Weekly Paclitaxel in Squamous NSCLC

Terminated Phase 2 Results posted Last updated 3 July 2018
What this trial tests

Phase 2 trial testing Open-label AZD2014 in Squamous Non Small Cell Lung Cancer in 11 participants. Terminated before completion.

Timeline
15 April 2015
Primary endpoint
29 December 2016
29 December 2016

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date15 April 2015
Primary completion29 December 2016
Estimated completion29 December 2016
Sites7 locations across United States, Germany, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Squamous Non Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes Primary · From first dose until disease progression (Approximately 3 months)

Calculation of the percentage of patient who have a Complete Response or Partial Response to treatment which is confirmed by a repeat assessment 4 weeks later

Complete Response (CR)
GroupValue95% CI
Open-label AZD201400 – 23.8
Partial Response (PR)
GroupValue95% CI
Open-label AZD201400 – 23.8
Number of Patients Who Experienced at Least One Adverse Event (AE) or Serious Adverse Event (SAE) Secondary · Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)

The safety and tolerability of AZD2014 with weekly paclitaxel as assessed with the collection of Adverse Events and Serious Adverse Events as reported during clinic visits. In addition, clinical assessments were made throughout the on treatment period including blood test for chemistry, haematology, and blood clotting. In addition to clinical observations such as vital signs, and cardiac function through the use of ECG. Any findings from the above assessments which were considered to be abnornal and clinically significant by the doctor were reported as (AEs or SAEs).

Adverse Event (AE)
GroupValue95% CI
Open-label AZD201411
Serious Adverse Event (SAE)
GroupValue95% CI
Open-label AZD20144
Overall Survival: Median Number of Days Between the First Dose and End of Life Due to Any Cause Secondary · From first dose until end of life (Approx 9 months)

Assessment of the duration of overall survival in weeks through direct patient follow-up. Any patient not known to have died at the time of analysis censored at the last recorded date the patient was known to be alive

GroupValue95% CI
Open-label AZD201410427 – 164
Best Objective Response: Number of Patients Who Experienced a Best Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not-Evaluable (NE), Through Measurement of Tumour Lesion Sizes. Secondary · From Baseline until Disease Progression (Approx 3 months)

Per Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed through imaging (CT or MRI scan) or clinical examination; Complete Response (CR): Disappearance of all target lesions; Partial Response (PR) \>=30% decrease in sum of target lesion longest diameter; Progressive Disease \>=20% increase in sum of target lesion longest diameter; Stable Disease (SD) increase or decrease amounting to neither PR or PD. Overall tumour assessment based on quantitative assessment of target lesions and qualitative assessment of non-target lesions in line with RECIST criteria.

PD
GroupValue95% CI
Open-label AZD20146
SD
GroupValue95% CI
Open-label AZD20145
PR
GroupValue95% CI
Open-label AZD20140
CR
GroupValue95% CI
Open-label AZD20140
Disease Control Rate: Percentage of Patients Who Achieve Partial Response, Complete Response or Stable Disease Through Assessment of Tumour Lesion Sizes Secondary · From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks

Assessment of the disease control rate, percentage of patients who experience a response through assessment of tumour lesions by RECIST 1.1 criteria

Disease Control Rate at 6 Weeks
GroupValue95% CI
Open-label AZD201445.524.1 – 68.2
Disease Control Rate at 13 Weeks
GroupValue95% CI
Open-label AZD201418.24.9 – 41.5
Disease Control Rate at 20 Weeks
GroupValue95% CI
Open-label AZD201418.24.9 – 41.5
Change in Tumour Size: Median Percentage Change in Tumour Size in mm by Measurement of Tumour Lesion Sizes Secondary · From baseline until documented progression (Approx 3 months)

Assessment of the degree of tumour response through measurement of the change in tumour lesion sizes

GroupValue95% CI
Open-label AZD20140.0-33.3 – 41.8
Progression Free Survival: Median Number of Days Between Start of Dosing Until Objective Disease Progression Through Measurement of Tumour Lesion Sizes Secondary · From date of first dose until documented progression or end of life (Approx 3 months)

Assessment of the duration of progression free survival through assessment of tumour lesions by RECIST 1.1 criteria

GroupValue95% CI
Open-label AZD20149115 – 98
Evaluate the Effect of the Combination of AZD2014 and Paclitaxel on Pharmacokinetics Assessment of Cmax Secondary · Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8

To determine the effect of co-administration of paclitaxel on the PK of oral AZD2014 and the effect of co administration of oral AZD2014 on the PK of paclitaxel (Group A) by: PK parameters for each in the presence and absence of the other by intensive PK sampling and NCA techniques.

Paclitaxel Cmax
GroupValue95% CI
Open-label AZD201422401500 – 2980
AZD2014 Cmax
GroupValue95% CI
Open-label AZD20141021741 – 1300

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected from the time of informed consent throughout the treatment period until the end of the follow-up period. The follow-up period if defined as 28 days after study treatment is discontinued for a given patient. Total duration of collection period = approximately 10 months if all cycles and follow-up period is completed.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Open-label AZD2014
Serious: 4/11 (36%)
Deaths: 9/11

Serious adverse events (7 terms)

ReactionSystemOpen-label AZD2014
CellulitisInfections and infestations
PneumoniaInfections and infestations
SeizureNervous system disorders
Deep vein thrombosisVascular disorders
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Other adverse events (48 terms — click to expand)

ReactionSystemOpen-label AZD2014
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Neuropathy PeripheralNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal PainGastrointestinal disorders
AstheniaGeneral disorders
PneumoniaInfections and infestations
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Fungal InfectionInfections and infestations
Lower Respiratory Tract InfectionInfections and infestations
NasopharyngitisInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Decreased AppetiteMetabolism and nutrition disorders
HypercalcaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Increased appetiteMetabolism and nutrition disorders
DepressionPsychiatric disorders
Eating disorder symptomPsychiatric disorders
InsomniaPsychiatric disorders
HeadacheNervous system disorders
Nerve compressionNervous system disorders
Dyspnoea ExertionalRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Nasal drynessRespiratory, thoracic and mediastinal disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Dry SkinSkin and subcutaneous tissue disorders
PapuleSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Cellulitis, Pneumonia, Seizure, Deep vein thrombosis, Acute Respiratory Failure, Pulmonary Embolism, Anaemia.

Data from ClinicalTrials.gov NCT02403895 adverse events section.

Sponsor's own description

Open--label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC)

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Intratumoral delivery of mTORC2-deficient dendritic cells inhibits B16 melanoma growth by promoting CD8(+) effector T cell responses.
    Raïch-Regué D, Fabian KP, Watson AR, Fecek RJ, et al · · 2016 · cited 22× · PMID 27471613 · DOI 10.1080/2162402x.2016.1146841

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