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NCT00890825

AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients

Completed Phase 2 Results posted Last updated 20 June 2018
What this trial tests

Phase 2 trial testing AZD6244 in Non Small Cell Lung Cancer in 88 participants. Completed in 2 November 2016.

Timeline
20 April 2009
Primary endpoint
11 May 2011
2 November 2016

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment88
Start date20 April 2009
Primary completion11 May 2011
Estimated completion2 November 2016
Sites63 locations across France, Italy, Peru, Belgium, Hungary, Mexico, Canada, Bulgaria

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with 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.

Overall Survival Primary · At least 12 months since start of treatment.

OS was calculated as the interval from the date of randomisation to the date of patient death (any cause). Patients who had not died at the time of the final analysis, or who withdrew consent, were censored at the last date the patient was known to be alive.

GroupValue95% CI
AZD6244 + Docetaxel29
Placebo + Docetaxel27
AZD6244 + Docetaxel13
Placebo + Docetaxel13
AZD6244 + Docetaxel1
Placebo + Docetaxel0
Progression Free Survival Secondary · At least 12 months after start of treatment

PFS was defined as the interval between the date of randomisation and the earlier date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression. Patients who did not progress or die at the time of analysis were censored at the time of their latest evaluable objective tumour assessment. This also included patients who withdrew consent.

GroupValue95% CI
AZD6244 + Docetaxel35
Placebo + Docetaxel36
AZD6244 + Docetaxel1
Placebo + Docetaxel2
AZD6244 + Docetaxel7
Placebo + Docetaxel2
Objective Response Rate Secondary · At least 12 months after start of treatment

ORR is defined as the ratio of proportions, patients with at least one visit response of CR or PR in AZD6244 + Docetaxel vs Placebo + Docetaxel.

GroupValue95% CI
AZD6244 + Docetaxel16
Placebo + Docetaxel0
AZD6244 + Docetaxel27
Placebo + Docetaxel40
Duration of Response Secondary · At least 12 months after start of treatment

Duration of response is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.

GroupValue95% CI
AZD6244 + Docetaxel193.4± 0.207
Placebo + DocetaxelNA± NA
Change From Baseline in Tumour Size at 6 Week. Secondary · 6 weeks after first dose of treatment

Percentage change from baseline in tumour size at 6 week. Values calculated as tumour sizes at 6 weeks minus value at baseline.

GroupValue95% CI
AZD6244 + Docetaxel-16.98-27.1 – -6.85
Placebo + Docetaxel0.05-9.84 – 9.93
Change From Baseline in Tumour Size at Week 12 Secondary · 12 weeks

Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline.

GroupValue95% CI
AZD6244 + Docetaxel-19.38-34.7 – -4.09
Placebo + Docetaxel6.62-8.31 – 21.54
Alive and Progression-Free at 6 Months Secondary · 6 months after first dose of treatment

Percentage of patients alive and progression-free at 6 months

GroupValue95% CI
AZD6244 + Docetaxel37.1
Placebo + Docetaxel15.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Over a minimum period of 12 months since start of treatment, or the date of the final analysis of the data, whichever is the later. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD6244 + Docetaxel
Serious: 26/44 (59%)
Deaths:
Placebo + Docetaxel
Serious: 13/42 (31%)
Deaths:

Serious adverse events (45 terms)

ReactionSystemAZD6244 + DocetaxelPlacebo + Docetaxel
Febrile neutropenaBlood and lymphatic system disorders
PneumoniaInfections and infestations
NeutropenaBlood and lymphatic system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Face oedemaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders
Lower respiratory tract infection bacterialInfections and infestations
CystitisInfections and infestations
EmpyemaInfections and infestations
InfluenzaInfections and infestations
Neutropenic infectionInfections and infestations
Respiratory tract infection viralInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Acute coronary syndromeCardiac disorders
Atrial flutterCardiac disorders
Cardiac arrestCardiac disorders
Pericardial effusionCardiac disorders
Other adverse events (32 terms — click to expand)

ReactionSystemAZD6244 + DocetaxelPlacebo + Docetaxel
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
AlopeciaSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Dysonoea exertionalRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
MyalgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Vision blurredEye disorders
DysgeusiaNervous system disorders
Neuropathy peripheralNervous system disorders
DehydrationMetabolism and nutrition disorders

Most-reported serious reactions: Febrile neutropena, Pneumonia, Neutropena, Respiratory failure, Interstitial lung disease, Pulmonary embolism, Face oedema, Back pain.

Data from ClinicalTrials.gov NCT00890825 adverse events section.

Sponsor's own description

The purpose of this study is to compare the efficacy of AZD6244 in combination with docetaxel versus docetaxel alone in patients with KRAS mutation positive locally advanced or metastatic non small cell lung cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study.
    Jänne PA, Shaw AT, Pereira JR, Jeannin G, et al · · 2013 · cited 493× · PMID 23200175 · DOI 10.1016/s1470-2045(12)70489-8
  2. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target.
    Román M, Baraibar I, López I, Nadal E, et al · · 2018 · cited 217× · PMID 29455666 · DOI 10.1186/s12943-018-0789-x
  3. MEK inhibitors for the treatment of non-small cell lung cancer.
    Han J, Liu Y, Yang S, Wu X, et al · · 2021 · cited 154× · PMID 33402199 · DOI 10.1186/s13045-020-01025-7
  4. The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma.
    Biernacka A, Tsongalis PD, Peterson JD, de Abreu FB, et al · · 2016 · cited 101× · PMID 27068338 · DOI 10.1016/j.cancergen.2016.03.001
  5. A RAS renaissance: emerging targeted therapies for KRAS-mutated non-small cell lung cancer.
    Vasan N, Boyer JL, Herbst RS. · · 2014 · cited 83× · PMID 24893629 · DOI 10.1158/1078-0432.ccr-13-1762
  6. The introduction of systematic genomic testing for patients with non-small-cell lung cancer.
    Cardarella S, Ortiz TM, Joshi VA, Butaney M, et al · · 2012 · cited 83× · PMID 23154547 · DOI 10.1097/jto.0b013e3182745bcb
  7. Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer.
    Jänne PA, Smith I, McWalter G, Mann H, et al · · 2015 · cited 59× · PMID 26125448 · DOI 10.1038/bjc.2015.215
  8. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines.
    Garon EB, Finn RS, Hosmer W, Dering J, et al · · 2010 · cited 54× · PMID 20587667 · DOI 10.1158/1535-7163.mct-10-0037

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Trials by the same sponsor.

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