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

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ClinicalTrials.gov Identifier: NCT00890825
Recruitment Status : Completed
First Posted : April 30, 2009
Results First Posted : June 20, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: AZD6244 Drug: docetaxel Drug: Placebo Phase 2

Detailed Description:

The primary objective of this study was to assess the efficacy in terms of overall survival (OS) of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC. Amendment 4 of the CSP altered the primary objective and outcome variable from progression-free survival (PFS) to OS, and the secondary outcome variable changed from OS to PFS.

The secondary objectives of the study were:

  • To further assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC
  • To assess the safety and tolerability profile of AZD6244 in combination with docetaxel
  • To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (cfDNA) for the analysis of KRAS mutation status
  • To investigate the PK of AZD6244 and N-desmethyl AZD6244 and any other known metabolites when AZD6244 is administered in combination with docetaxel.

The exploratory objectives of the study were:

  • To assess the prevalence, severity and change over time of advanced NSCLC cancer specific symptoms in patients receiving AZD6244 in combination with docetaxel and docetaxel alone
  • To explore potential biomarkers in residual tumour, plasma and/or serum taken for KRAS mutational analysis which may influence development of NSCLC (and associated clinical characteristics) and/or response (optional)
  • To investigate the relationship between AZD6244 and/or N-desmethyl AZD6244 and any other known metabolite plasma concentrations or exposure and clinical outcomes, efficacy, AEs, and/or safety parameters if deemed appropriate
  • To collect and store deoxyribonucleic acid (DNA), derived from a blood sample, for future exploratory research into genes that may influence response, eg, distribution, safety, tolerability, and efficacy of AZD6244 and/or agents used in combination and/or as comparators (optional).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 in Combination With Docetaxel, Compared With Docetaxel Alone, in 2nd Line Patients With KRAS Mutation Positive Locally Advanced Metastatic NSCLC
Actual Study Start Date : April 20, 2009
Actual Primary Completion Date : May 11, 2011
Actual Study Completion Date : November 2, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Active Comparator: AZD6244 + Docetaxel
AZD6244 75 mg bd + Docetaxel 75 mg/m^2
Drug: AZD6244
oral capsules, 75mg twice daily
Other Name: Selumetinib

Drug: docetaxel
75mg/m2 iv on day 1 of every 21 day cycle
Other Name: Taxotere

Placebo Comparator: Placebo + Docetaxel
Placebo + Docetaxel 75 mg/m^2
Drug: docetaxel
75mg/m2 iv on day 1 of every 21 day cycle
Other Name: Taxotere

Drug: Placebo
placebo




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 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.


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 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.

  2. Objective Response Rate [ Time Frame: 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.

  3. Duration of Response [ Time Frame: 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.

  4. Change From Baseline in Tumour Size at 6 Week. [ Time Frame: 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.

  5. Change From Baseline in Tumour Size at Week 12 [ Time Frame: 12 weeks ]
    Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline.

  6. Alive and Progression-Free at 6 Months [ Time Frame: 6 months after first dose of treatment ]
    Percentage of patients alive and progression-free at 6 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally advanced or metastatic non small cell lung cancer (IIIB-IV)
  • Failure of first line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) in advanced disease or subsequent relapse of disease following first line therapy
  • Tumour sample confirmed as KRAS mutation positive (Note: Sample must be available upon enrolment to ship to AZ appointed central laboratory, or mutation status confirmed locally at AstraZeneca agreed local laboratory using agreed methodology, or mutation status confirmed by an accredited (eg CLIA certified) commercial laboratory (eg Genzyme or Lab 21).

Exclusion Criteria:

  • Received >1 prior anti-cancer therapy for advanced or metastatic non small cell lung cancer (excluding radiotherapy)
  • Prior treatment with a MEK inhibitor or any docetaxel containing regimen (prior treatment with paclitaxel is acceptable)
  • Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug
  • Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00890825


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Locations
United States, California
Research Site
Los Angeles, California, United States, 90095
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02115
United States, Ohio
Research Site
Columbus, Ohio, United States, 43210
Belgium
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Brussels, Belgium, 1090
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Charleroi, Belgium, 6000
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Edegem, Belgium, 2650
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Leuven, Belgium, 3000
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Liege, Belgium, B-4000
Research Site
Liège, Belgium, 4000
Brazil
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Belo Horizonte, Brazil, 30180-090
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Ijuí, Brazil, 98700-000
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Porto Alegre, Brazil, 90610-000
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Rio de Janeiro, Brazil, 20230-130
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Santo André, Brazil, 09060-650
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Sao Paulo, Brazil, 01221-020
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Sao Paulo, Brazil, 04023-062
Research Site
Sao Paulo, Brazil, 04530-001
Bulgaria
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Plovdiv, Bulgaria, 4000
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Sofia, Bulgaria, 1233
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Sofia, Bulgaria, 1527
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Sofia, Bulgaria, 1756
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Sofia, Bulgaria, 1784
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Varna, Bulgaria, 9010
Canada, Ontario
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Oshawa, Ontario, Canada, L1G 2B9
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Ottawa, Ontario, Canada, K1H 8L6
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Toronto, Ontario, Canada, M5G 2M9
Czechia
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Ostrava, Czechia, 708 52
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Praha 8, Czechia, 180 81
Research Site
Znojmo, Czechia, 669 02
France
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Brest Cedex, France, 29609
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Clermont Ferrand, France, 63003
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Dijon, France, 21034
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Lyon Cedex 08, France, 69373
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Marseille, France, 13015
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Rennes Cedex 9, France, 35033
Hungary
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Budapest, Hungary, 1032
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Budapest, Hungary, 1121
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Budapest, Hungary, 1122
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Budapest, Hungary, 1125
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Györ, Hungary, 9024
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Mosdós, Hungary, 7257
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Székesfehérvár, Hungary, 8000
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Törökbálint, Hungary, 2045
Italy
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Bologna, Italy, 40131
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Genova, Italy, 16100
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Milano, Italy, 20162
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Orbassano, Italy, 10043
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Perugia, Italy, 06132
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Roma, Italy, 00144
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Rozzano, Italy, 20089
Mexico
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Mexico, Mexico, 14080
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Morelia, Mexico, 58000
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Zacatecas, Mexico, 98000
Peru
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Lima, Peru, LIMA 11
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Lima, Peru, LIMA 27
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Lima, Peru, LIMA 33
Research Site
Lima, Peru, LIMA 41
Spain
Research Site
A Coruña, Spain, 15006
Research Site
Badalona(Barcelona), Spain, 08916
Research Site
Barcelona, Spain, 08028
Research Site
Madrid, Spain, 28041
Research Site
Malaga, Spain, 29010
Research Site
Málaga, Spain, 29010
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Dr. Pasi Janne Dana-Farber Cancer Institute, Boston, USA
Study Director: Dr. Gabriella Mariani AstraZeneca, Hertfordshire, UK

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00890825     History of Changes
Other Study ID Numbers: D1532C00016
First Posted: April 30, 2009    Key Record Dates
Results First Posted: June 20, 2018
Last Update Posted: June 20, 2018
Last Verified: May 2018

Keywords provided by AstraZeneca:
Non small cell lung cancer (NSCLC)
KRAS mutation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action