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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

April 29, 2009
April 30, 2009
June 14, 2017
June 20, 2018
June 20, 2018
April 20, 2009
May 11, 2011   (Final data collection date for primary outcome measure)
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.
To assess the efficacy in terms of Progression Free Survival (PFS) of AZD6244 in combination with docetaxel compared with docetaxel alone, in 2nd line patients with KRAS mutation positive locally advanced or metastatic non small cell lung cancer [ Time Frame: PFS will be assessed using RECIST measurements. RECIST assessments to be carried out at baseline, week 6, week 12 and every 12 weeks thereafter relative to randomisation ]
Complete list of historical versions of study NCT00890825 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • To further assess the efficacy in terms of:- Overall Survival (OS)- Objective Response Rate (ORR)- Duration of Response (DoR)- Change in tumour size at 12 weeks- Alive and Progression Free at 6 months (APF6) [ Time Frame: ORR, DoR, APF6 and change in tumour size at 12 weeks will be assessed using RECIST measurements. RECIST assessments to be carried out at baseline, week 6, week 12 and every 12 weeks thereafter relative to randomisation ]
  • To assess the safety and tolerability profile of AZD6244 in combination with docetaxel [ Time Frame: At every visit (ie weekly for the first 6 weeks and then every 3 weeks) ]
  • To investigate the pharmacokinetics of AZD6244 [ Time Frame: At Day 1 and Day 22 ]
Not Provided
Not Provided
 
AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients
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
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.

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).
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Non Small Cell Lung Cancer
  • 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
  • Drug: Placebo
    placebo
  • Active Comparator: AZD6244 + Docetaxel
    AZD6244 75 mg bd + Docetaxel 75 mg/m^2
    Interventions:
    • Drug: AZD6244
    • Drug: docetaxel
  • Placebo Comparator: Placebo + Docetaxel
    Placebo + Docetaxel 75 mg/m^2
    Interventions:
    • Drug: docetaxel
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
88
80
November 2, 2016
May 11, 2011   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 130 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Brazil,   Bulgaria,   Canada,   Czechia,   France,   Hungary,   Italy,   Mexico,   Peru,   Spain,   United States
Czech Republic,   Denmark,   Luxembourg
 
NCT00890825
D1532C00016
No
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Not Provided
Principal Investigator: Dr. Pasi Janne Dana-Farber Cancer Institute, Boston, USA
Study Director: Dr. Gabriella Mariani AstraZeneca, Hertfordshire, UK
AstraZeneca
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP