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

May 22, 2018 updated by: AstraZeneca

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1090
        • Research Site
      • Charleroi, Belgium, 6000
        • Research Site
      • Edegem, Belgium, 2650
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
      • Liege, Belgium, B-4000
        • Research Site
      • Liège, Belgium, 4000
        • Research Site
  • Brazil
      • Belo Horizonte, Brazil, 30180-090
        • Research Site
      • Ijuí, Brazil, 98700-000
        • Research Site
      • Porto Alegre, Brazil, 90610-000
        • Research Site
      • Rio de Janeiro, Brazil, 20230-130
        • Research Site
      • Santo André, Brazil, 09060-650
        • Research Site
      • Sao Paulo, Brazil, 01221-020
        • Research Site
      • Sao Paulo, Brazil, 04023-062
        • Research Site
      • Sao Paulo, Brazil, 04530-001
        • Research Site
  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • Research Site
      • Sofia, Bulgaria, 1784
        • Research Site
      • Sofia, Bulgaria, 1527
        • Research Site
      • Sofia, Bulgaria, 1233
        • Research Site
      • Sofia, Bulgaria, 1756
        • Research Site
      • Varna, Bulgaria, 9010
        • Research Site
  • Canada
    • Ontario
      • Oshawa, Ontario, Canada, L1G 2B9
        • Research Site
      • Ottawa, Ontario, Canada, K1H 8L6
        • Research Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Site
  • Czechia
      • Ostrava, Czechia, 708 52
        • Research Site
      • Praha 8, Czechia, 180 81
        • Research Site
      • Znojmo, Czechia, 669 02
        • Research Site
  • France
      • Brest Cedex, France, 29609
        • Research Site
      • Clermont Ferrand, France, 63003
        • Research Site
      • Dijon, France, 21034
        • Research Site
      • Lyon Cedex 08, France, 69373
        • Research Site
      • Marseille, France, 13015
        • Research Site
      • Rennes Cedex 9, France, 35033
        • Research Site
  • Hungary
      • Budapest, Hungary, 1121
        • Research Site
      • Budapest, Hungary, 1125
        • Research Site
      • Budapest, Hungary, 1122
        • Research Site
      • Budapest, Hungary, 1032
        • Research Site
      • Györ, Hungary, 9024
        • Research Site
      • Mosdós, Hungary, 7257
        • Research Site
      • Székesfehérvár, Hungary, 8000
        • Research Site
      • Törökbálint, Hungary, 2045
        • Research Site
  • Italy
      • Bologna, Italy, 40131
        • Research Site
      • Genova, Italy, 16100
        • Research Site
      • Milano, Italy, 20162
        • Research Site
      • Orbassano, Italy, 10043
        • Research Site
      • Perugia, Italy, 06132
        • Research Site
      • Roma, Italy, 00144
        • Research Site
      • Rozzano, Italy, 20089
        • Research Site
  • Mexico
      • Mexico, Mexico, 14080
        • Research Site
      • Morelia, Mexico, 58000
        • Research Site
      • Zacatecas, Mexico, 98000
        • Research Site
  • Peru
      • Lima, Peru, LIMA 27
        • Research Site
      • Lima, Peru, LIMA 41
        • Research Site
      • Lima, Peru, LIMA 11
        • Research Site
      • Lima, Peru, LIMA 33
        • Research Site
  • Spain
      • 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
        • Research Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: AZD6244 + Docetaxel
AZD6244 75 mg bd + Docetaxel 75 mg/m^2
Drug: AZD6244
oral capsules, 75mg twice daily
Other Names:
  • Selumetinib
Drug: docetaxel
75mg/m2 iv on day 1 of every 21 day cycle
Other Names:
  • Taxotere
PLACEBO_COMPARATOR: Placebo + Docetaxel
Placebo + Docetaxel 75 mg/m^2
Drug: Placebo
placebo
Drug: docetaxel
75mg/m2 iv on day 1 of every 21 day cycle
Other Names:
  • Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At least 12 months since start of treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At least 12 months after start of treatment
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.
At least 12 months after start of treatment
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.
At least 12 months after start of treatment
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.
6 weeks after first dose of treatment
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.
12 weeks
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
6 months after first dose of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Dr. Pasi Janne, Dana-Farber Cancer Institute, Boston, USA
  • Study Director: Dr. Gabriella Mariani, AstraZeneca, Hertfordshire, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 20, 2009

Primary Completion (ACTUAL)

May 11, 2011

Study Completion (ACTUAL)

November 2, 2016

Study Registration Dates

First Submitted

April 29, 2009

First Submitted That Met QC Criteria

April 29, 2009

First Posted (ESTIMATE)

April 30, 2009

Study Record Updates

Last Update Posted (ACTUAL)

June 20, 2018

Last Update Submitted That Met QC Criteria

May 22, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D1532C00016

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non Small Cell Lung Cancer

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belgium

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe